Saurabh Gawde

All Publications

• BTK Inhibition Resets Pathological B and T cell Subsets in Patients with IgG4-Related Disease Lanz, T., Gawde, S., Baker, M. OXFORD UNIV PRESS. 2026

  View details for DOI 10.1093/jimmun/vkag141.629

  View details for Web of Science ID 001834295400001

• Exploring Female Obesity and Type 1 Interferon Signaling in the Context of Multiple Sclerosis Testut, M., Axtell, R., Gawde, S., Kumar, G., Massey, K., Pardo, G. OXFORD UNIV PRESS. 2026

  View details for DOI 10.1093/jimmun/vkag141.1742

  View details for Web of Science ID 001834224000001

• Zanubrutinib monotherapy for IgG4-related head and neck disease. Annals of the rheumatic diseases Baker, M. C., Gawde, S., Horomanski, A., Fairchild, R. M., Liu, Y., Mikelov, A., Sun, Y., Vitale, M. R., Maestri, E., Held, F., Deluna, M., Park, W. G., Siddiqi, H., Taylor, L., Bopardikar, S., Khalighi, M., Franc, B. L., Penta, M., Boyd, S. D., Khatri, P., Zhu, H., Pham, N., Guja, K. E., Lanz, T. V. 2026

  Abstract

  Immunoglobulin (Ig) G4-related disease (IgG4-RD) is commonly treated with glucocorticoids and B-cell depletion, but cumulative toxicity and relapse underscore the need for alternative approaches. We evaluated the efficacy, safety, and immunological effects of Bruton's tyrosine kinase (BTK) inhibition with zanubrutinib in active IgG4-RD.In this phase 2, open-label, proof-of-concept trial, 10 participants with lacrimal and submandibular gland IgG4-RD received zanubrutinib 80 mg twice daily for up to 24 weeks without glucocorticoid induction or background immunosuppression. The primary endpoint was change in lacrimal and submandibular gland volume at week 24 by blinded fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (evaluable n = 8). Secondary endpoints included metabolic imaging parameters, clinical disease activity, serologic biomarkers, and safety. Single-cell RNA sequencing with immune repertoire profiling was performed to define cellular mechanisms.At week 24, mean gland volume decreased by 46.7% (lacrimal) and 29.9% (submandibular) (both P = .008), with concordant reductions in total lesion glycolysis (-91.6 g; P = .05) and total metabolic lesion volume (-20.7 cm³; P = .05). Clinical disease activity improved (IgG4-RD Responder Index -6.0 points; P = .01), alongside reductions in serum IgG4 (-417 mg/dL; P = .008) and circulating plasmablasts. Imaging and serologic changes were strongly correlated. Single-cell analyses demonstrated treatment-associated modulation of B-cell transcriptional programmes, reductions in IgG4-skewed plasmablasts, and attenuation of cytotoxic CD4⁺ T cells. Adverse events were predominantly mild; 1 serious event (COVID-19) occurred off treatment.Zanubrutinib monotherapy produced substantial imaging-defined and clinical improvements in active glandular IgG4-RD without glucocorticoid induction. BTK inhibition was associated with modulation of B-cell differentiation states and downstream immune programmes, supporting its development as a steroid-sparing, non-B-cell-depleting therapeutic strategy.

  View details for DOI 10.1016/j.ard.2026.06.020

  View details for PubMedID 42448495

• A Phase II, Single-site, Open-label Study of Zanubrutinib in Patients with igg4-related Disease Baker, M., Horomanski, A., Fairchild, R., Liu, Y., Deluna, M., Lanz, T., Gawde, S., Khalighi, M., Franc, B., Penta, M., Pham, N., Guja, K. WILEY. 2025: 2286-2288

  View details for Web of Science ID 001671398102334

• Distinct Reactivity Patterns to EBV Nuclear Proteins and CNS Antigens Distinguish CNS Demyelinating Disorders from Systemic Autoimmunity Sattarnezhad, N., Held, F., Babaei, M., Gawde, S., Ho, P., Barrett, A., Wijerante, T., Comanescu, A., Parsafar, S., Bartels, F., McDonald, J., Kipp, L., Van Haren, K., Chaichian, Y., Lock, C., Han, M., Baker, M., Dunn, J., Steinman, L., Lanz, T., Robinson, W. SAGE PUBLICATIONS LTD. 2025: 309-310

  View details for Web of Science ID 001603659901013

• Obesity intensifies sex-specific interferon signaling to selectively worsen central nervous system autoimmunity in females. Cell metabolism Cordeiro, B., Ahn, J. J., Gawde, S., Ucciferri, C., Alvarez-Sanchez, N., Revelo, X. S., Stickle, N., Massey, K., Brooks, D. G., Guthridge, J. M., Pardo, G., Winer, D. A., Axtell, R. C., Dunn, S. E. 2024; 36 (10): 2298-2314.e11

  Abstract

  Obesity has been implicated in the rise of autoimmunity in women. We report that obesity induces a serum protein signature that is associated with T helper 1 (Th1), interleukin (IL)-17, and multiple sclerosis (MS) signaling pathways selectively in human females. Females, but not male mice, subjected to diet-induced overweightness/obesity (DIO) exhibited upregulated Th1/IL-17 inflammation in the central nervous system during experimental autoimmune encephalomyelitis, a model of MS. This was associated with worsened disability and a heightened expansion of myelin-specific Th1 cells in the peripheral lymphoid organs. Moreover, at steady state, DIO increased serum levels of interferon (IFN)-α and potentiated STAT1 expression and IFN-γ production by naive CD4+ T cells uniquely in female mice. This T cell phenotype was driven by increased adiposity and was prevented by the removal of ovaries or knockdown of the type I IFN receptor in T cells. Our findings offer a mechanistic explanation of how obesity enhances autoimmunity.

  View details for DOI 10.1016/j.cmet.2024.07.017

  View details for PubMedID 39168127

  View details for PubMedCentralID PMC11463735

• Serum Proteomics Distinguish Subtypes of NMO Spectrum Disorder and MOG Antibody-Associated Disease and Highlight Effects of B-Cell Depletion. Neurology(R) neuroimmunology & neuroinflammation Gawde, S., Siebert, N., Ruprecht, K., Kumar, G., Ko, R. M., Massey, K., Guthridge, J. M., Mao-Draayer, Y., Schindler, P., Hastermann, M., Pardo, G., Paul, F., Axtell, R. C. 2024; 11 (4): e200268

  Abstract

  AQP4 antibody-positive NMOSD (AQP4-NMOSD), MOG antibody-associated disease (MOGAD), and seronegative NMOSD (SN-NMOSD) are neuroautoimmune conditions that have overlapping clinical manifestations. Yet, important differences exist in these diseases, particularly in B-cell depletion (BCD) efficacy. Yet, the biology driving these differences remains unclear. Our study aims to clarify biological pathways distinguishing these diseases beyond autoantibodies and investigate variable BCD effects through proteomic comparisons.In a retrospective study, 1,463 serum proteins were measured in 53 AQP4-NMOSD, 25 MOGAD, 18 SN-NMOSD, and 49 healthy individuals. To identify disease subtype-associated signatures, we examined serum proteins in patients without anti-CD20 B-cell depletion (NoBCD). We then assessed the effect of BCD treatment within each subtype by comparing proteins between BCD-treated and NoBCD-treated patients.In NoBCD-treated patients, serum profiles distinguished the 3 diseases. AQP4-NMOSD showed elevated type I interferon-induced chemokines (CXCL9 and CXCL10) and TFH chemokine (CXCL13). MOGAD exhibited increased cytotoxic T-cell proteases (granzyme B and granzyme H), while SN-NMOSD displayed elevated Wnt inhibitory factor 1, a marker for nerve injury. Across all subtypes, BCD-treated patients showed reduction of B-cell-associated proteins. In AQP4-NMOSD, BCD led to a decrease in several inflammatory pathways, including IL-17 signaling, cytokine storm, and macrophage activation. By contrast, BCD elevated these pathways in patients with MOGAD. BCD had no effect on these pathways in SN-NMOSD.Proteomic profiles show unique biological pathways that distinguish AQP4-NMOSD, MOGAD, or SN-NMOSD. Furthermore, BCD uniquely affects inflammatory pathways in each disease type, providing an explanation for the disparate therapeutic response in AQP4-NMOSD and MOGAD.

  View details for DOI 10.1212/NXI.0000000000200268

  View details for PubMedID 38885457

  View details for PubMedCentralID PMC11186702

• Biomarker panel increases accuracy for identification of an MS relapse beyond sNfL. Multiple sclerosis and related disorders Gawde, S., Agasing, A., Bhatt, N., Toliver, M., Kumar, G., Massey, K., Nguyen, A., Mao-Draayer, Y., Macwana, S., DeJager, W., Guthridge, J. M., Pardo, G., Dunn, J., Axtell, R. C. 2022; 63: 103922

  Abstract

  BACKGROUND: For relapsing-remitting multiple sclerosis (RRMS), there is a need for biomarker development beyond clinical manifestations and MRI. Soluble neurofilament light chain (sNfL) has emerged as a biomarker for inflammatory activity in RRMS. However, there are limitations to the accuracy of sNfL in identifying relapses. Here, we sought to identify a panel of biomarkers that would increase the precision of distinguishing patients in relapse compared to sNfL alone.METHODS: We used a multiplex approach to measure levels of 724 blood proteins in two distinct RRMS cohorts. Multiple t-tests with covariate correction determined biomarkers that were differentially regulated in relapse and remission. Logistic regression models determined the accuracy of biomarkers to distinguish relapses from remission.RESULTS: The discovery cohort identified 37 proteins differentially abundant in active RRMS relapse compared to remission. The verification cohort confirmed four proteins, including sNfL, were altered in active RRMS relapse compared to remission. Logistic regression showed that the 4-protein panel identified active relapse with higher accuracy (AUC=0.87) than sNfL alone (AUC=0.69).CONCLUSION: Our studies confirmed that sNfL is elevated during relapses in RRMS patients. Furthermore, we identified three other blood proteins, uPA, hK8 and DSG3 that were altered during relapse. Together, these four biomarkers could be used to monitor disease activity in RRMS patients.

  View details for DOI 10.1016/j.msard.2022.103922

  View details for PubMedID 35671674

• Transcriptomics and proteomics reveal a cooperation between interferon and T-helper 17 cells in neuromyelitis optica. Nature communications Agasing, A. M., Wu, Q., Khatri, B., Borisow, N., Ruprecht, K., Brandt, A. U., Gawde, S., Kumar, G., Quinn, J. L., Ko, R. M., Mao-Draayer, Y., Lessard, C. J., Paul, F., Axtell, R. C. 2020; 11 (1): 2856

  Abstract

  Type I interferon (IFN-I) and T helper 17 (TH17) drive pathology in neuromyelitis optica spectrum disorder (NMOSD) and in TH17-induced experimental autoimmune encephalomyelitis (TH17-EAE). This is paradoxical because the prevalent theory is that IFN-I inhibits TH17 function. Here we report that a cascade involving IFN-I, IL-6 and B cells promotes TH17-mediated neuro-autoimmunity. In NMOSD, elevated IFN-I signatures, IL-6 and IL-17 are associated with severe disability. Furthermore, IL-6 and IL-17 levels are lower in patients on anti-CD20 therapy. In mice, IFN-I elevates IL-6 and exacerbates TH17-EAE. Strikingly, IL-6 blockade attenuates disease only in mice treated with IFN-I. By contrast, B-cell-deficiency attenuates TH17-EAE in the presence or absence of IFN-I treatment. Finally, IFN-I stimulates B cells to produce IL-6 to drive pathogenic TH17 differentiation in vitro. Our data thus provide an explanation for the paradox surrounding IFN-I and TH17 in neuro-autoimmunity, and may have utility in predicting therapeutic response in NMOSD.

  View details for DOI 10.1038/s41467-020-16625-7

  View details for PubMedID 32503977

  View details for PubMedCentralID PMC7275086

• B cell function impacts the efficacy of IFN-β therapy in EAE. Journal of neuroimmunology Agasing, A. M., Gawde, S., Kumar, G., Turner, E., Axtell, R. C. 2020; 338: 577106

  Abstract

  Recent studies identified that interferon beta (IFN-β) treatment skews B-cells towards a regulatory phenotype in multiple sclerosis. To assess B cell involvement during IFN-β therapy, we compared IFN-β treatment in a B cell-independent model and a B cell-dependent model of experimental autoimmune encephalomyelitis (EAE). We show that in B cell-independent EAE, IFN-β ameliorates neuroinflammation. Conversely, in B cell-dependent EAE, IFN-β has no effect on disease. Effective IFN-β therapy in B cell-independent EAE was associated with reduced inflammatory T cells in the CNS and skewed splenic B cells towards an immature population and away from a germinal center population. These immune cell populations were unchanged in B cell-dependent EAE. Finally, we found that IFN-β increased marginal zone B cells in both EAE models. These findings indicate that B cell function impacts IFN-β efficacy during neuroinflammation.

  View details for DOI 10.1016/j.jneuroim.2019.577106

  View details for PubMedID 31715458

  View details for PubMedCentralID PMC6911824