Matthew C. Baker, MD MS

All Publications

• Increased risk of osteoarthritis in patients with atopic disease. Annals of the rheumatic diseases Baker, M. C., Sheth, K., Lu, R., Lu, D., von Kaeppler, E. P., Bhat, A., Felson, D. T., Robinson, W. H. 2023

  Abstract

  To determine the incidence of osteoarthrits (OA) in patients with atopic disease compared with matched non-exposed patients.We conducted a retrospective cohort study with propensity score matching using claims data from Optum's de-identified Clinformatics Data Mart (CDM) (January 2003 to June 2019) and electronic health record data from the Stanford Research Repository (STARR) (January 2010 to December 2020). We included adult patients without pre-existing OA or inflammatory arthritis who were exposed to atopic disease or who were non-exposed. The primary outcome was the development of incident OA.In Optum CDM, we identified 117 346 exposed patients with asthma or atopic dermatitis (mean age 52 years; 60% female) and 1 247 196 non-exposed patients (mean age 50 years; 48% female). After propensity score matching (n=1 09 899 per group), OA incidence was higher in patients with asthma or atopic dermatitis (26.9 per 1000 person-years) compared with non-exposed patients (19.1 per 1000 person-years), with an adjusted odds ratio (aOR) of 1.58 (95% CI 1.55 to 1.62) for developing OA. This effect was even more pronounced in patients with both asthma and atopic dermatitis compared with non-exposed patients (aOR=2.15; 95% CI 1.93 to 2.39) and in patients with asthma compared with patients with chronic obstructive pulmonary disease (aOR=1.83; 95% CI 1.73 to 1.95). We replicated our results in an independent dataset (STARR), which provided the added richness of body mass index data. The aOR of developing OA in patients with asthma or atopic dermatitis versus non-exposed patients in STARR was 1.42 (95% CI 1.36 to 1.48).This study demonstrates an increased incidence of OA in patients with atopic disease. Future interventional studies may consider targeting allergic pathways for the prevention or treatment of OA.

  View details for DOI 10.1136/ard-2022-223640

  View details for PubMedID 36987654

• Sarcoidosis rates in BCG-vaccinated and unvaccinated young adults: A natural experiment using Danish registers. Seminars in arthritis and rheumatism Baker, M. C., Vágó, E., Tamang, S., Horváth-Puhó, E., Sørensen, H. T. 2023; 60: 152205

  Abstract

  Sarcoidosis may have an infectious trigger, including Mycobacterium spp. The Bacille Calmette-Guérin (BCG) vaccine provides partial protection against tuberculosis and induces trained immunity. We examined the incidence rate (IR) of sarcoidosis in Danish individuals born during high BCG vaccine uptake (born before 1976) compared with individuals born during low BCG vaccine uptake (born in or after 1976).We performed a quasi-randomized registry-based incidence study using data from the Danish Civil Registration System and the Danish National Patient Registry between 1995 and 2016. We included individuals aged 25-35 years old and born between 1970 and 1981. Using Poisson regression models, we calculated the incidence rate ratio (IRR) of sarcoidosis in individuals born during low BCG vaccine uptake versus high BCG vaccine uptake, adjusting for age and calendar year (separately for men and women).The IR of sarcoidosis was increased for individuals born during low BCG vaccine uptake compared with individuals born during high BCG vaccine uptake, which was largely attributed to men. The IRR of sarcoidosis for men born during low BCG vaccine uptake versus high BCG vaccine uptake was 1.22 (95% confidence interval [CI] 1.02-1.45). In women, the IRR was 1.08 (95% CI 0.88-1.31).In this quasi-experimental study that minimizes confounding, the time period with high BCG vaccine uptake was associated with a lower incidence rate of sarcoidosis in men, with a similar effect seen in women that did not reach significance. Our findings support a potential protective effect of BCG vaccination against the development of sarcoidosis. Future interventional studies for high-risk individuals could be considered.

  View details for DOI 10.1016/j.semarthrit.2023.152205

  View details for PubMedID 37054583

• Development of Osteoarthritis in Adults With Type 2 Diabetes Treated With Metformin vs a Sulfonylurea. JAMA network open Baker, M. C., Sheth, K., Liu, Y., Lu, D., Lu, R., Robinson, W. H. 2023; 6 (3): e233646

  Abstract

  Importance: Metformin may have a protective association against developing osteoarthritis (OA), but robust epidemiological data are lacking.Objective: To determine the risk of OA and joint replacement in individuals with type 2 diabetes treated with metformin compared with a sulfonylurea.Design, Setting, and Participants: This retrospective cohort study used claims data from the Optum deidentified Clinformatics Data Mart Database between December 2003 and December 2019. Participants included individuals aged 40 years or older with at least 1 year of continuous enrollment and type 2 diabetes. Individuals with type 1 diabetes or a prior diagnosis of OA, inflammatory arthritis, or joint replacement were excluded. Time-conditional propensity score matching was conducted using age, sex, race, Charlson comorbidity score, and treatment duration to create a prevalent new-user cohort. Data were analyzed from April to December 2021.Exposures: Treatment with metformin or a sulfonylurea.Main Outcomes and Measures: The outcomes of interest were incident OA and joint replacement. Cox proportional hazard models were used to calculate adjusted hazard ratios (aHRs) of incident OA and joint replacement. In a sensitivity analysis, individuals only ever treated with metformin were compared with individuals only ever treated with a sulfonylurea, allowing for longer-term follow up of the outcome (even after stopping the medication of interest).Results: After time-conditional propensity score matching, the metformin and control groups each included 20 937 individuals (mean [SD] age 62.0 [11.5] years; 24 379 [58.2%] males). In the adjusted analysis, the risk of developing OA was reduced by 24% for individuals treated with metformin compared with a sulfonylurea (aHR, 0.76; 95% CI, 0.68-0.85; P<.001), but there was no significant difference for risk of joint replacement (aHR, 0.80; 95% CI, 0.50-1.27; P=.34). In the sensitivity analysis, the risk of developing OA remained lower in individuals treated with metformin compared with a sulfonylurea (aHR, 0.77; 95% CI, 0.65-0.90; P<.001) and the risk of joint replacement remained not statistically significant (aHR, 1.04; 95% CI, 0.60-1.82; P=.89).Conclusions and Relevance: In this cohort study of individuals with diabetes, metformin treatment was associated with a significant reduction in the risk of developing OA compared with sulfonylurea treatment. These results further support preclinical and observational data that suggest metformin may have a protective association against the development of OA; future interventional studies with metformin for the treatment or prevention of OA should be considered.

  View details for DOI 10.1001/jamanetworkopen.2023.3646

  View details for PubMedID 36939700

• Incidence of Interstitial Lung Disease in Patients With Rheumatoid Arthritis Treated With Biologic and Targeted Synthetic Disease-Modifying Antirheumatic Drugs. JAMA network open Baker, M. C., Liu, Y., Lu, R., Lin, J., Melehani, J., Robinson, W. H. 2023; 6 (3): e233640

  Abstract

  Importance: Current data are lacking regarding the risk of biologic and targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) use on the development of interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA).Objective: To determine the risk of developing ILD in patients with RA undergoing treatment with different b/tsDMARDs.Design, Setting, and Participants: Retrospective cohort study using claims data from the Optum Clinformatics Data Mart between December 2003 and December 2019. Adult patients with RA, 1 year or more of continuous enrollment, treatment with a b/tsDMARD of interest, and without preexisting ILD were included. Data were analyzed from October 2021 to April 2022.Exposures: New administration of adalimumab, abatacept, rituximab, tocilizumab, or tofacitinib.Main Outcomes and Measures: Crude incidence rates (IRs) for the development of ILD were calculated. The risk of ILD across different b/tsDMARDs was compared using Cox-regression models. A sensitivity analysis using a prevalent new-user cohort design compared patients treated with tofacitinib and adalimumab.Results: A total of 28 559 patients with RA (mean [SD] age 55.6 [13.7] years; 22 158 female [78%]) were treated with adalimumab (13 326 patients), abatacept (5676 patients), rituximab (5444 patients), tocilizumab (2548 patients), or tofacitinib (1565 patients). Crude IRs per 1000 person-years for ILD were 3.43 (95% CI 2.85-4.09) for adalimumab, 4.46 (95% CI 3.44-5.70) for abatacept, 6.15 (95% CI 4.76-7.84) for rituximab, 5.05 (95% CI 3.47-7.12) for tocilizumab, and 1.47 (95% CI 0.54-3.27) for tofacitinib. After multiple adjustments, compared with patients treated with adalimumab, patients treated with tofacitinib had a lower risk of ILD (adjusted hazard ratio [aHR] 0.31; 95% CI, 0.12-0.78; P=.009). In a prevalent new-user cohort analysis, patients treated with tofacitinib had 68% reduced risk of ILD compared with adalimumab (aHR 0.32; 95% CI 0.13-0.82; P<.001). In an adjusted model, there was a 69% reduced risk of ILD in patients treated with tofacitinib compared with patients treated with adalimumab.Conclusions and Relevance: In this retrospective cohort of patients with RA, patients treated with tofacitinib had the lowest incidence of ILD compared with patients treated with all bDMARDs evaluated, and patients treated with tofacitinib had a reduced risk of ILD compared with patients treated with adalimumab after adjusting for important covariates. Additional prospective studies are needed to better understand the role tofacitinib may play in preventing ILD in patients with RA. These results, while significant, should be interpreted with caution given the fairly small sample size of the tofacitinib group.

  View details for DOI 10.1001/jamanetworkopen.2023.3640

  View details for PubMedID 36939701

• The Positive Predictive Value of a Very High Serum IgG4 Concentration for the Diagnosis of IgG4-Related Disease. The Journal of rheumatology Baker, M. C., Cook, C., Fu, X., Perugino, C. A., Stone, J. H., Wallace, Z. S. 2022

  Abstract

  OBJECTIVE: Serum IgG4 concentrations are used to evaluate a diagnosis of IgG4- related disease (IgG4-RD), but the positive predictive value (PPV) of a very high IgG4 level is uncertain. This study evaluated the PPV of a very high IgG4 concentration for diagnosing IgG4-RD.METHODS: The data warehouses of two large academic healthcare systems were queried for IgG4 concentration test results. Cases with serum IgG4 concentrations >5x upper limit of normal (ULN) were included. Cases of IgG4-RD were determined using the ACR/EULAR Classification Criteria. The PPV for IgG4-RD of an IgG4 concentration >5x was estimated. Other conditions associated with very high IgG4 concentrations and specific features of IgG4-RD cases were characterized.RESULTS: IgG4 concentrations were available in 32,206 cases. Of these, 3,039 (9.4%) had elevated IgG4 concentrations, and a final cohort of 191 (0.6%) cases had IgG4 concentrations >5x ULN (median age 66 years, 72% male). The PPV of an IgG4 concentration >5x ULN for a diagnosis of IgG4-RD was 75.4% (95% CI 68.7-81.3). In the remaining cases, elevated IgG4 concentrations were observed among patients with malignancies, autoimmune diseases, and infections.CONCLUSION: The majority of cases with serum IgG4 concentrations >5x ULN in this study had IgG4-RD. These data support the high weight placed on very high serum IgG4 concentrations in the ACR/EULAR Classification Criteria. However, 25% of cases with very high IgG4 concentrations had an alternative diagnosis, underscoring the importance of considering the broad differential of etiologies associated with an elevated IgG4 concentration when evaluating a patient.

  View details for DOI 10.3899/jrheum.220423

  View details for PubMedID 36319016

• The Third Dose Is the Charm: Effective Cellular and Humoral Immune Responses to Third COVID-19 Vaccine Doses in Immunosuppressed Nonresponders. The Journal of rheumatology Kuswanto, W., Baker, M. C. 2022

  Abstract

  Pathogens drive an effective immune response by stimulating the innate immune system, leading to activation of host T and B cells.1 Subsequent pathogen exposure leads to a more robust response through memory T and B cells.

  View details for DOI 10.3899/jrheum.220960

  View details for PubMedID 36243410

• Sarcoidosis incidence after mTOR inhibitor treatment. Seminars in arthritis and rheumatism Baker, M. C., Vago, E., Liu, Y., Lu, R., Tamang, S., Horvath-Puho, E., Sorensen, H. T. 2022; 57: 152102

  Abstract

  OBJECTIVE: Mechanistic target of rapamycin (mTOR) inhibitors are effective in animal models of granulomatous disease, but their benefit in sarcoidosis patients is unknown. We evaluated the incidence of sarcoidosis in patients treated with mTOR inhibitors versus calcineurin inhibitors.METHODS: This was a cohort study using the Optum Clinformatics Data Mart (CDM) Database (2003-2019), IBM MarketScan Research Database (2006-2016), and Danish health and administrative registries (1996-2018). Patients aged ≥18 years with ≥1 year continuous enrollment before and after kidney, liver, heart, or lung transplant treated with an mTOR inhibitor or calcineurin inhibitor were included. Patients diagnosed with sarcoidosis before, or up to 90 days after, transplant were excluded. The incidence of sarcoidosis by treatment group was calculated.RESULTS: In the Optum CDM/IBM MarketScan cohort, 1,898 patients were treated with an mTOR inhibitor (mean age 49 years; 34% female) and 9,894 patients were treated with a calcineurin inhibitor (mean age 50 years; 37% female). The mean follow-up in the mTOR inhibitor group was 1.1 years, with no incident sarcoidosis diagnosed. In the calcineurin inhibitor group, the mean follow-up was 2.2 years, with 12 incident sarcoidosis cases diagnosed. In the Danish cohort, 230 patients were treated with an mTOR inhibitor (mean age 49; 45% female), with no incident sarcoidosis diagnosed. There were 3,411 patients treated with a calcineurin inhibitor (mean age 45; 40% female), with 10 incident cases of sarcoidosis diagnosed.CONCLUSIONS: This study indicates a potential protective effect of mTOR inhibitor treatment compared with calcineurin inhibitor treatment against the development of sarcoidosis.

  View details for DOI 10.1016/j.semarthrit.2022.152102

  View details for PubMedID 36182721

• Reduction in Rheumatoid Arthritis-Associated Interstitial Lung Disease Risk in Patients Treated with Tofacitinib Baker, M., Liu, Y., Lu, R., Lin, J., Melehani, J., Robinson, W. WILEY. 2022: 4476-4478

  View details for Web of Science ID 000877386506227

• Sarcoidosis in patients after solid organ transplantation treated with mtor inhibitors versus calcineurin inhibitors Vago, E. K., Baker, M. C., Tamang, S., Sorensen, H., Horvath-Puho, E. WILEY. 2022: 263-264

  View details for Web of Science ID 000859084401127

• Sarcoidosis Incidence After mTOR Inhibitor Treatment Baker, M., Vago, E., Liu, Y., Lu, R., Tamang, S., Horvath-Puho, E., Sorensen, H. WILEY. 2022: 254-256

  View details for Web of Science ID 000877386500136

• Sarcoidosis Rates in BCG-Vaccinated and Unvaccinated Young Adults: A Danish Register-Based Study Baker, M., Vago, E., Tamang, S., Horvath-Puho, E., Sorensen, H. WILEY. 2022: 2207-2208

  View details for Web of Science ID 000877386502125

• Preparing for the next pandemic via transfer learning from existing diseases with hierarchical multi-modal BERT: a study on COVID-19 outcome prediction. Scientific reports Agarwal, K., Choudhury, S., Tipirneni, S., Mukherjee, P., Ham, C., Tamang, S., Baker, M., Tang, S., Kocaman, V., Gevaert, O., Rallo, R., Reddy, C. K. 2022; 12 (1): 10748

  Abstract

  Developing prediction models for emerging infectious diseases from relatively small numbers of cases is a critical need for improving pandemic preparedness. Using COVID-19 as an exemplar, we propose a transfer learning methodology for developing predictive models from multi-modal electronic healthcare records by leveraging information from more prevalent diseases with shared clinical characteristics. Our novel hierarchical, multi-modal model ([Formula: see text]) integrates baseline risk factors from the natural language processing of clinical notes at admission, time-series measurements of biomarkers obtained from laboratory tests, and discrete diagnostic, procedure and drug codes. We demonstrate the alignment of [Formula: see text]'s predictions with well-established clinical knowledge about COVID-19 through univariate and multivariate risk factor driven sub-cohort analysis. [Formula: see text]'s superior performance over state-of-the-art methods shows that leveraging patient data across modalities and transferring prior knowledge from similar disorders is critical for accurate prediction of patient outcomes, and this approach may serve as an important tool in the early response to future pandemics.

  View details for DOI 10.1038/s41598-022-13072-w

  View details for PubMedID 35750878

• Prevalence of autoimmunity and atopy in US adults with glioblastoma and meningioma. Neuro-oncology Ostrom, Q. T., Lu, D., Lu, R., Baker, M. C. 2022

  View details for DOI 10.1093/neuonc/noac145

  View details for PubMedID 35713330

• Development of a natural language processing system for extracting rheumatoid arthritis outcomes from clinical notes using the national RISE registry. Arthritis care & research Humbert-Droz, M., Izadi, Z., Schmajuk, G., Gianfrancesco, M., Baker, M. C., Yazdany, J., Tamang, S. 2022

  Abstract

  OBJECTIVE: To accelerate the use of outcome measures in rheumatology, we developed and evaluated a natural language processing (NLP) pipeline for extracting these measures from free-text outpatient rheumatology notes within the ACR's Rheumatology Informatics System for Effectiveness (RISE) registry.METHODS: We included all patients in RISE (2015 to 2018). The NLP pipeline extracted scores corresponding to eight measures of RA disease activity (DA) and functional status (FS) documented in outpatient rheumatology notes. Score extraction performance was evaluated by chart review, and we assessed agreement with scores documented in structured data. We conducted an external validation of our NLP pipeline using data from rheumatology notes from an academic medical center that is not included in the RISE registry.RESULTS: We processed over 34 million notes from 854,628 patients, 158 practices, and 24 EHR systems from RISE. Manual chart review revealed a sensitivity, positive predictive value (PPV), and F1 score of 95%, 87%, and 91%, respectively. Substantial agreement was observed between scores extracted from RISE notes and scores derived from structured data (kappa: 0.43 - 0.68 among DA and 0.86-0.98 among FS measures). Inthe external validation, we found a sensitivity, PPV, and F1 score of 92%, 69%, and 79%, respectively.CONCLUSIONS: We developed an NLP pipeline to extract RA outcome measures from a national registry of notes from multiple EHR systems and found it to have good internal and external validity. This pipeline can facilitate measurement of clinical and patient reported outcomes for use in research and quality measurement.

  View details for DOI 10.1002/acr.24869

  View details for PubMedID 35157365

• Increased double-negative alpha beta plus T cells reveal adult-onset autoimmune lymphoproliferative syndrome in a patient with IgG4-related disease HAEMATOLOGICA Brar, N., Spinner, M. A., Baker, M. C., Advani, R. H., Natkunam, Y., Lewis, D. B., Silva, O. 2022; 107 (1): 347-350

  View details for DOI 10.3324/haematol.2021.279297

  View details for Web of Science ID 000740550800043

• Effective Viral Vector SARS-CoV-2 Booster Vaccination in a Patient with Rheumatoid Arthritis after Initial Ineffective mRNA Vaccine Response. Arthritis & rheumatology (Hoboken, N.J.) Baker, M. C., Mallajosyula, V., Davis, M. M., Boyd, S. D., Nadeau, K. C., Robinson, W. H. 2021

  Abstract

  Managing patients with rheumatic disease during the COVID-19 pandemic has posed a unique challenge. Immunosuppressed patients are at an increased risk for developing severe COVID-19 and may not derive full protection from the vaccine (1-5). Thus, it is paramount we develop strategies whereby rheumatic disease patients can be protected from the pandemic virus and its variants.

  View details for DOI 10.1002/art.41978

  View details for PubMedID 34514750

• Metformin Use Reduces the Risk of Developing Osteoarthritis: A Propensity Score Matching Study Sheth, K., Lu, D., Lu, R., Robinson, W., Baker, M. WILEY. 2021: 994-996

  View details for Web of Science ID 000744545201237

• Osteoarthritis Risk Is Increased in Patients with Atopic Disease Baker, M., Sheth, K., Lu, R., Lu, D., von Kaeppler, E., Bhat, A., Felson, D., Robinson, W. WILEY. 2021: 2351-2353

  View details for Web of Science ID 000744545204174

• Disease Associations with Very High Serum IgG4 Concentrations: A Retrospective Multi-Center Study Baker, M., Cook, C., Fu, X., Perugino, C., Stone, J., Wallace, Z. WILEY. 2021: 2290-2292

  View details for Web of Science ID 000744545204143

• Comparison of Adverse Events Among Home- vs Facility-Administered Biologic Infusions, 2007-2017. JAMA network open Baker, M. C., Weng, Y., Fairchild, R., Ahuja, N., Rohatgi, N. 2021; 4 (6): e2110268

  Abstract

  Importance: Infusion reactions occur in 7% to 20% of patients receiving biologics. Home infusions are convenient and incur lower costs but may be associated with more adverse events; the safety of receiving biologic infusions for immune-mediated diseases at home remains unclear.Objective: To assess whether patients receiving home biologic infusions have increased adverse events requiring emergency department (ED) or hospital admission compared with patients receiving facility infusions.Design, Setting, and Participants: This retrospective cohort study used administrative claims data from a large national insurer for adult patients who received biologic infusions for immune-mediated disease between January 2007 and December 2017. Patients with hematologic malignant neoplasms or bone marrow transplantation were excluded. Data were analyzed from August 2019 to October 2020.Main Outcomes and Measures: ED or hospital admission on the same or next day after administration of a biologic infusion at home vs at a facility; secondary outcomes included discontinuation of the biologic after an ED or hospital admission and postinfusion mortality.Results: Of a total of 57 220 patients (mean [SD] age, 50.1 [14.8] years; 512 314 [68.1%] women) who received 752 150 biologic infusions (34 078 home infusions [4.5%] to 3954 patients and 718 072 facility infusions [95.5%] to 54 770 patients), patients who received home infusions were younger (mean [SD] age, 43.2 [13.2] vs 51.3 [14.8] years), more likely to be men (14 031 [41.2%] vs 225 668 [31.4%]), and had a lower Charlson comorbidity score compared with patients who received facility infusions (mean [SD] score, 0.5 [1.0] vs 1.1 [1.3]). Home infusions were associated with 25% increased odds of ED or hospital admission on the same or next day after the infusion (odds ratio [OR], 1.25; 95% CI, 1.09-1.44; P=.002) and 28% increased odds of discontinuation of the biologic after the ED or hospital admission (OR, 1.28; 95% CI, 1.08-1.51; P=.005). There was no difference in postinfusion mortality between home or facility infusions. The rates of adverse events were highest with home infusions of tocilizumab (48 of 481 infusions [10.0%]), vedolizumab (150 of 2681 infusions [5.6%]), and infliximab (1085 of 20 653 infusions [5.3%]), although the number of tocilizumab and vedolizumab infusions was low.Conclusions and Relevance: In this study, biologic infusions administered at home, compared with those administered at a facility, were associated with increased adverse events requiring escalation of care. Because the number of home infusions has increased and is expected to continue to rise, the safety implications of administering biologic infusions at home needs to be further assessed.

  View details for DOI 10.1001/jamanetworkopen.2021.10268

  View details for PubMedID 34081140

• Neutralizing Anti-Interleukin-1 Receptor-Antagonist Autoantibodies Induce Inflammatory and Fibrotic Mediators in IgG4-Related Disease. The Journal of allergy and clinical immunology Jarrell, J. A., Baker, M. C., Perugino, C. A., Liu, H., Bloom, M. S., Maehara, T., Wong, H. H., Lanz, T., Adamska, J. Z., Kongpachith, S., Sokolove, J., Stone, J. H., Pillai, S. S., Robinson, W. H. 2021

  Abstract

  BACKGROUND: IgG4-related disease (IgG4-RD) is a fibro-inflammatory condition involving loss of B cell tolerance and production of autoantibodies. However, the relevant targets and role of these aberrant humoral immune responses are not defined.OBJECTIVE: To identify novel autoantibodies and autoantigen targets that promote pathogenic responses in IgG4-RD.METHODS: We sequenced plasmablast antibody repertoires in patients with IgG4-RD. Representative monoclonal antibodies (mAb) were expressed and their specificities characterized using cytokine microarrays. The role of anti-interleukin-1 receptor-antagonist (IL-1RA) autoantibodies was investigated using in vitro assays.RESULTS: We identified strong reactivity against human IL-1RA using a clonally-expanded plasmablast-derived mAb from a patient with IgG4-RD. IgG4-RD patient plasma exhibited elevated levels of reactivity against IL-1RA compared to controls and neutralized IL-1RA activity, resulting in inflammatory and fibrotic mediator production in vitro. IL-1RA was detected in lesional tissues from IgG4-RD patients. Patients with anti-IL-1RA autoantibodies of the IgG4 subclass had greater numbers of organs affected than those without anti-IL-1RA autoantibodies. Peptide analyses identified IL-1RA epitopes targeted by anti-IL-1RA antibodies at sites near the IL-1RA/IL-1R interface. Serum from patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) also had elevated levels of anti-IL-1RA autoantibodies compared to controls.CONCLUSION: A subset of patients with IgG4-RD have anti-IL-1RA autoantibodies, which promote pro-inflammatory and pro-fibrotic meditator production via IL-1RA neutralization. These findings support a novel immunological mechanism underlying the pathogenesis of IgG4-RD. Anti-IL-1RA autoantibodies are also present in a subset of patients with SLE and RA, suggesting a potential common pathway in multiple autoimmune diseases.

  View details for DOI 10.1016/j.jaci.2021.05.002

  View details for PubMedID 33974929

• Non-invasive vagus nerve stimulation for rheumatoid arthritis: a proof-of-concept study LANCET RHEUMATOLOGY Marsal, S., Corominas, H., Jose de Agustin, J., Perez-Garcia, C., Lopez-Lasanta, M., Borrell, H., Reina, D., Sanmarti, R., Narvaez, J., Franco-Jarava, C., Peterfy, C., Antonio Narvaez, J., Sharma, V., Alataris, K., Genovese, M. C., Baker, M. C. 2021; 3 (4): E262-E269

  View details for DOI 10.1016/S2665-9913(20)30425-2

  View details for Web of Science ID 000644477400012

• Prevalence and significance of pulmonary disease on lung ultrasonography in outpatients with SARS-CoV-2 infection. BMJ open respiratory research Fairchild, R. M., Horomanski, A., Mar, D. A., Triant, G. R., Lu, R., Lu, D., Guo, H. H., Baker, M. C. 2021; 8 (1)

  Abstract

  The majority of patients with SARS-CoV-2 infection are diagnosed and managed as outpatients; however, little is known about the burden of pulmonary disease in this setting. Lung ultrasound (LUS) is a convenient tool for detection of COVID-19 pneumonia. Identifying SARS-CoV-2 infected outpatients with pulmonary disease may be important for early risk stratification.To investigate the prevalence, natural history and clinical significance of pulmonary disease in outpatients with SARS-CoV-2.SARS-CoV-2 PCR positive outpatients (CV(+)) were assessed with LUS to identify the presence of interstitial pneumonia. Studies were considered positive based on the presence of B-lines, pleural irregularity and consolidations. A subset of patients underwent longitudinal examinations. Correlations between LUS findings and patient symptoms, demographics, comorbidities and clinical outcomes over 8 weeks were evaluated.102 CV(+) patients underwent LUS with 42 (41%) demonstrating pulmonary involvement. Baseline LUS severity scores correlated with shortness of breath on multivariate analysis. Of the CV(+) patients followed longitudinally, a majority showed improvement or resolution in LUS findings after 1-2 weeks. Only one patient in the CV(+) cohort was briefly hospitalised, and no patient died or required mechanical ventilation.We found a high prevalence of LUS findings in outpatients with SARS-CoV-2 infection. Given the pervasiveness of pulmonary disease across a broad spectrum of LUS severity scores and lack of adverse outcomes, our findings suggest that LUS may not be a useful as a risk stratification tool in SARS-CoV-2 in the general outpatient population.

  View details for DOI 10.1136/bmjresp-2021-000947

  View details for PubMedID 34385149

  View details for PubMedCentralID PMC8361701

• Non-invasive Vagus Nerve Stimulation Improves Signs and Symptoms of Rheumatoid Arthritis: Results of a Pilot Study Marsal, S., Corominas, H., De Agustin De Oro, J., Perez Garcia, C., Lopez Lasanta, M., Borrell, H., Reina, D., Sanmarti, R., Javier Narvaez, F., Franco-Jarava, C., Peterfy, C., Antonio Narvaez, J., Sharma, V., Alataris, K., Genovese, M., Baker, M. WILEY. 2020

  View details for Web of Science ID 000587568506246

• CD52 Is Elevated on B cells of SLE Patients and Regulates B Cell Function. Frontiers in immunology Bhamidipati, K. n., Silberstein, J. L., Chaichian, Y. n., Baker, M. C., Lanz, T. V., Zia, A. n., Rasheed, Y. S., Cochran, J. R., Robinson, W. H. 2020; 11: 626820

  Abstract

  Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by B cell dysregulation and breaks in tolerance that lead to the production of pathogenic autoantibodies. We performed single-cell RNA sequencing of B cells from healthy donors and individuals with SLE which revealed upregulated CD52 expression in SLE patients. We further demonstrate that SLE patients exhibit significantly increased levels of B cell surface CD52 expression and plasma soluble CD52, and levels of soluble CD52 positively correlate with measures of lupus disease activity. Using CD52-deficient JeKo-1 cells, we show that cells lacking surface CD52 expression are hyperresponsive to B cell receptor (BCR) signaling, suggesting an inhibitory role for the surface-bound protein. In healthy donor B cells, antigen-specific BCR-activation initiated CD52 cleavage in a phospholipase C dependent manner, significantly reducing cell surface levels. Experiments with recombinant CD52-Fc showed that soluble CD52 inhibits BCR signaling in a manner partially-dependent on Siglec-10. Moreover, incubation of unstimulated B cells with CD52-Fc resulted in the reduction of surface immunoglobulin and CXCR5. Prolonged incubation of B cells with CD52 resulted in the expansion of IgD+IgMlo anergic B cells. In summary, our findings suggest that CD52 functions as a homeostatic protein on B cells, by inhibiting responses to BCR signaling. Further, our data demonstrate that CD52 is cleaved from the B cell surface upon antigen engagement, and can suppress B cell function in an autocrine and paracrine manner. We propose that increased expression of CD52 by B cells in SLE represents a homeostatic mechanism to suppress B cell hyperactivity.

  View details for DOI 10.3389/fimmu.2020.626820

  View details for PubMedID 33658999

  View details for PubMedCentralID PMC7917337

• Phase II, randomised, double-blind, multicentre study evaluating the safety and efficacy of filgotinib and lanraplenib in patients with lupus membranous nephropathy. RMD open Baker, M. n., Chaichian, Y. n., Genovese, M. n., Derebail, V. n., Rao, P. n., Chatham, W. n., Bubb, M. n., Lim, S. n., Hajian, H. n., Gurtovaya, O. n., Patel, U. n., Tumlin, J. n. 2020; 6 (3)

  Abstract

  Patients with lupus membranous nephropathy (LMN) are at risk for prolonged proteinuria and progressive chronic kidney disease. There are no proven effective treatments for LMN, and controlled trials are lacking. This trial assessed the preferential Janus kinase 1 (JAK1) inhibitor filgotinib and the spleen tyrosine kinase inhibitor lanraplenib in patients with LMN.This was a phase II, randomised, double-blind trial conducted at 15 centres in the USA to evaluate the safety and efficacy of filgotinib or lanraplenib for the treatment of LMN. Eligible patients were randomised 1:1 to receive either filgotinib or lanraplenib in a blinded fashion for up to 52 weeks. The primary endpoint was the per cent change in 24-hour urine protein from baseline to week 16.Nine patients were randomised to receive filgotinib (n=5) or lanraplenib (n=4). Four patients in the filgotinib group and one patient in the lanraplenib group completed week 16. There was a median reduction of 50.7% in 24-hour urine protein after 16 weeks of treatment with filgotinib (n=4), and the median Systemic Lupus Erythematosus Disease Activity Index from the Safety of Estrogens in Lupus National Assessment score remained stable. Filgotinib treatment was well tolerated. Limited conclusions can be drawn about treatment with lanraplenib.The number of patients treated in this study was small, and only limited conclusions can be drawn. There may be a therapeutic benefit with filgotinib treatment, which may support future investigations with filgotinib or other JAK inhibitors in patients with LMN.NCT03285711.

  View details for DOI 10.1136/rmdopen-2020-001490

  View details for PubMedID 33380521

• Osteoarthritis risk is reduced after treatment with ticagrelor compared to clopidogrel: a propensity score matching analysis. Arthritis & rheumatology (Hoboken, N.J.) Baker, M. C., Weng, Y. n., William, R. H., Ahuja, N. n., Rohatgi, N. n. 2020

  Abstract

  Osteoarthritis (OA) is a common cause of joint pain and disability, and effective treatments are lacking. Extracellular adenosine has anti-inflammatory effects and can prevent and treat OA in animal models. Ticagrelor and clopidogrel are both used in patients with coronary artery disease, but only ticagrelor increases extracellular adenosine. The aim of this study was to determine whether treatment with ticagrelor was associated with a lower risk of OA.We conducted a 1:2 propensity score matching analysis using the Optum Clinformatics™ Data Mart from 2011 to 2017. We included patients who received either ticagrelor or clopidogrel for at least 90 days and excluded those with a prior diagnosis of OA or inflammatory arthritis. OA was identified using International Classification of Diseases codes. The primary outcome was the time to diagnosis of OA after treatment with ticagrelor versus clopidogrel.Our propensity score matched cohort consisted of 7,007 ticagrelor-treated patients and 14,014 clopidogrel-treated patients, with a median number of days on treatment of 287 and 284 respectively. For both groups, the mean age was 64 years, and 73% of the patients were male. Multivariate Cox-regression analysis estimated a hazard ratio of 0.71 (95% CI 0.64-0.79, p<0.001) for developing OA after treatment with ticagrelor compared to clopidogrel.Treatment with ticagrelor was associated with a 29% lower risk of developing OA compared to clopidogrel over five years of follow-up. We hypothesize that the reduction in OA seen in patients who received ticagrelor may in part be due to increased extracellular adenosine.

  View details for DOI 10.1002/art.41412

  View details for PubMedID 32564514

• A Mortality Risk Score Model for Clinically Amyopathic Dermatomyositis-Associated Interstitial Lung Disease: Will It Have the Necessary "FLAIR" to Improve Clinical Outcomes? Chest Baker, M. C., Chung, L. n., Fiorentino, D. F. 2020; 158 (4): 1307–9

  View details for DOI 10.1016/j.chest.2020.06.001

  View details for PubMedID 33036075

• Dermatomyositis Associated With a Skull Base Chondrosarcoma JCR-JOURNAL OF CLINICAL RHEUMATOLOGY Baker, M. C., Smith, G. P., Miloslavsky, E. M. 2019; 25 (4): E50–E53

  View details for DOI 10.1097/RHU.0000000000000732

  View details for Web of Science ID 000470908400009

• TNF-alpha inhibition for the treatment of cardiac sarcoidosis. Seminars in arthritis and rheumatism Baker, M. C., Sheth, K. n., Witteles, R. n., Genovese, M. C., Shoor, S. n., Simard, J. F. 2019

  Abstract

  Tumor necrosis factor alpha (TNF-α) inhibitors are increasingly being used for treating refractory cardiac sarcoidosis. There is a theoretical risk, however, that these therapies can worsen heart failure, and reports on efficacy and safety are lacking.We conducted a retrospective review of all cardiac sarcoidosis patients seen at Stanford University from 2009 to 2018. Data were collected on patient demographics, diagnostic testing, and treatment outcomes.We identified 77 cardiac sarcoidosis patients, of which 20 (26%) received TNF-α inhibitor treatment. The majority were treated for progressive heart failure or tachyarrhythmia, along with worsening imaging findings. All TNF-α inhibitor treated patients demonstrated meaningful benefit, as assessed by changes in advanced imaging, echocardiographic measures of cardiac function, and prednisone use.A large cohort (n = 77) of cardiac sarcoidosis patients has been treated at Stanford University. Roughly one-fourth of these patients (n = 20) received TNF-α inhibitors. Of these patients, none had worsening heart failure and all saw clinical benefit. These results help support the use of TNF-α inhibitors for the treatment of cardiac sarcoidosis based on real-world evidence and highlight the need for future prospective studies.

  View details for DOI 10.1016/j.semarthrit.2019.11.004

  View details for PubMedID 31806154

• Security and Privacy Qualities of Medical Devices: An Analysis of FDA Postmarket Surveillance PLOS ONE Kramer, D. B., Baker, M., Ransford, B., Molina-Markham, A., Stewart, Q., Fu, K., Reynolds, M. R. 2012; 7 (7)

  Abstract

  Medical devices increasingly depend on computing functions such as wireless communication and Internet connectivity for software-based control of therapies and network-based transmission of patients' stored medical information. These computing capabilities introduce security and privacy risks, yet little is known about the prevalence of such risks within the clinical setting.We used three comprehensive, publicly available databases maintained by the Food and Drug Administration (FDA) to evaluate recalls and adverse events related to security and privacy risks of medical devices.Review of weekly enforcement reports identified 1,845 recalls; 605 (32.8%) of these included computers, 35 (1.9%) stored patient data, and 31 (1.7%) were capable of wireless communication. Searches of databases specific to recalls and adverse events identified only one event with a specific connection to security or privacy. Software-related recalls were relatively common, and most (81.8%) mentioned the possibility of upgrades, though only half of these provided specific instructions for the update mechanism.Our review of recalls and adverse events from federal government databases reveals sharp inconsistencies with databases at individual providers with respect to security and privacy risks. Recalls related to software may increase security risks because of unprotected update and correction mechanisms. To detect signals of security and privacy problems that adversely affect public health, federal postmarket surveillance strategies should rethink how to effectively and efficiently collect data on security and privacy problems in devices that increasingly depend on computing systems susceptible to malware.

  View details for DOI 10.1371/journal.pone.0040200

  View details for Web of Science ID 000306956300012

  View details for PubMedID 22829874

  View details for PubMedCentralID PMC3400651

• Enhancement of DNA tumor vaccine efficacy by gene gun-mediated codelivery of threshold amounts of plasmid-encoded helper antigen BLOOD Leitner, W. W., Baker, M. C., Berenberg, T. L., Lu, M. C., Yannie, P. J., Udey, M. C. 2009; 113 (1): 37-45

  Abstract

  Nucleic acid-based vaccines are effective in infectious disease models but have yielded disappointing results in tumor models when tumor-associated self-antigens are used. Incorporation of helper epitopes from foreign antigens into tumor vaccines might enhance the immunogenicity of DNA vaccines without increasing toxicity. However, generation of fusion constructs encoding both tumor and helper antigens may be difficult, and resulting proteins have unpredictable physical and immunologic properties. Furthermore, simultaneous production of equal amounts of highly immunogenic helper and weakly immunogenic tumor antigens in situ could favor development of responses against the helper antigen rather than the antigen of interest. We assessed the ability of 2 helper antigens (beta-galactosidase or fragment C of tetanus toxin) encoded by one plasmid to augment responses to a self-antigen (lymphoma-associated T-cell receptor) encoded by a separate plasmid after codelivery into skin by gene gun. This approach allowed adjustment of the relative ratios of helper and tumor antigen plasmids to optimize helper effects. Incorporation of threshold (minimally immunogenic) amounts of helper antigen plasmid into a DNA vaccine regimen dramatically increased T cell-dependent protective immunity initiated by plasmid-encoded tumor-associated T-cell receptor antigen. This simple strategy can easily be incorporated into future vaccine trials in experimental animals and possibly in humans.

  View details for DOI 10.1182/blood-2008-01-136267

  View details for Web of Science ID 000262162800010

  View details for PubMedID 18832136

  View details for PubMedCentralID PMC2614641