Vivian Saper, MD

All Publications

• Interleukin(IL)-1/IL-6-inhibitor-associated drug reaction with eosinophilia and systemic symptoms (DReSS) in systemic inflammatory illnesses. The journal of allergy and clinical immunology. In practice Saper, V. E., Tian, L., Verstegen, R. H., Conrad, C. K., Cidon, M., Hopper, R. K., Kuo, C. S., Osoegawa, K., Baszis, K., Bingham, C. A., Ferguson, I., Hahn, T., Horne, A., Isupova, E. A., Jones, J. T., Kasapcopur, Ö., Klein-Gitelman, M. S., Kostik, M. M., Ozen, S., Phadke, O., Prahalad, S., Randell, R. L., Sener, S., Stingl, C., Abdul-Aziz, R., Akoghlanian, S., Al Julandani, D., Alvarez, M. B., Bader-Meunier, B., Balay-Dustrude, E. E., Balboni, I., Baxter, S. K., Berard, R. A., Bhattad, S., Bolaria, R., Boneparth, A., Cassidy, E. A., Co, D. O., Collins, K. P., Dancey, P., Dickinson, A. M., Edelheit, B. S., Espada, G., Flanagan, E. R., Imundo, L. F., Jindal, A. K., Kim, H. A., Klaus, G., Lake, C., Lapin, W. B., Lawson, E. F., Marmor, I., Mombourquette, J., Ogunjimi, B., Olveda, R., Ombrello, M. J., Onel, K., Poholek, C., Ramanan, A. V., Ravelli, A., Reinhardt, A., Robinson, A. D., Rouster-Stevens, K., Saad, N., Schneider, R., Selmanovic, V., Pasic, I. S., Shenoi, S., Shilo, N. R., Soep, J. B., Sura, A., Taber, S. F., Tesher, M., Tibaldi, J., Torok, K. S., Tsin, C. M., Vasquez-Canizares, N., Villacis Nunez, D. S., Way, E. E., Whitehead, B., Zemel, L. S., Sharma, S., Fernández-Viña, M. A., Mellins, E. D. 2024

  Abstract

  After introducing interleukin(IL)-1/IL-6 inhibitors, some Still and Still-like patients developed unusual often fatal pulmonary disease. This complication was associated with scoring as DReSS (drug reaction with eosinophilia and systemic symptoms) implicating these inhibitors, although DReSS can be difficult to recognize in the setting of systemic inflammatory disease.We sought to facilitate recognition of IL-1/IL-6 inhibitor-DReSS in systemic inflammatory illnesses (Still/Still-like) by looking at timing and reaction-associated features. We evaluated outcomes of stopping or not-stopping IL-1/IL-6-inhibitors after DReSS reaction began.In an international study collaborating primarily with pediatric specialists, we characterized features of 89 drug-reaction cases versus 773 drug-exposed controls and compared outcomes of 52 cases stopping IL-1/IL-6-inhibitors to 37 cases not-stopping these drugs.Before reaction began, drug-reaction cases and controls were clinically comparable, except for younger disease onset age for reaction cases with pre-existing cardiothoracic comorbidities. After reaction began, increased rates of pulmonary complications and macrophage activation syndrome (MAS), differentiated drug-reaction cases from drug-tolerant controls (p=4.7x10-35; p=1.1x10-24, respectively). Initial DReSS feature was typically reported 2-8 weeks after initiating IL-1/IL-6-inhibition. In drug-reaction cases stopping versus not-stopping IL-1/IL-6-inhibitor treatment, reaction related features were indistinguishable, including pulmonary complication rates [75%(39/52] versus [76%(28/37)]. Those stopping subsequently required fewer medications for treatment of systemic inflammation, had decreased rates of MAS, and improved survival (p=0.005, multivariate regression). Resolution of pulmonary complications occurred in 67%(26/39) of drug-reaction cases who stopped and in none who continued inhibitors.In systemic inflammatory illnesses, recognition of IL-1/IL-6-inhibitor-associated reactions followed by avoidance of IL-1/IL-6-inhibitors significantly improved outcomes.

  View details for DOI 10.1016/j.jaip.2024.07.002

  View details for PubMedID 39002722

• Severe delayed hypersensitivity reactions to IL-1 and IL-6 inhibitors link to common HLA-DRB1*15 alleles. Annals of the rheumatic diseases Saper, V. E., Ombrello, M. J., Tremoulet, A. H., Montero-Martin, G., Prahalad, S., Canna, S., Shimizu, C., Deutsch, G., Tan, S. Y., Remmers, E. F., Monos, D., Hahn, T., Phadke, O. K., Cassidy, E., Ferguson, I., Mallajosyula, V., Xu, J., Rosa Duque, J. S., Chua, G. T., Ghosh, D., Szymanski, A. M., Rubin, D., Burns, J. C., Tian, L., Fernandez-Vina, M. A., Mellins, E. D., Hollenbach, J. A., Drug Hypersensitivity Consortium, INCHARGE Consortium, Aziz, R. A., Berard, R., Bingham, C. A., Bonaparth, A. D., Casey, A., Collins, K. P., Cidon, M., Goodman, S. I., Grom, A. A., Hazen, M., Hoftman, A., Ibarra, M., Jerath, R., Kingsbury, D. J., Klein-Gitelman, M. S., Lai, K., Lapidus, S., Mendoza-Londono, R., Onel, K., Perez, M., Radhakrishna, S. M., Reinhardt, A., Riskalla, M., Roth, J., Rosenwasser, N., Saad, N., Schulert, G. S., Shenoi, S., Smith, J. A., Soep, J., Stingl, C., Stoll, M. L., Tesher, M., Whitehead, B., Zemel, L., Anton, J., Bohnsack, J. F., Cobb, J., Demirkaya, E., Foell, D., Gattorno, M., Grom, A., Hilario, M. O., Ilowite, N. T., Haas, J., Hinks, A., Kastner, D. L., Langfeld, C. D., Martini, A., Mellins, E. D., Minden, K., Oliveira, S., Ombrello, M. J., Ozen, S., Prahalad, S., Rosen-Wolff, A., Rosenberg, A., Russo, R., Signa, S., Tachmazidou, I., Tenbrock, K., Thompson, S., Thomson, W., Wedderburn, L. R., Woo, P., Yeung, R. S., Zeft, A. S., Len, C. 2021

  Abstract

  OBJECTIVES: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe, delayed hypersensitivity reaction (DHR). We observed DRESS to inhibitors of interleukin 1 (IL-1) or IL-6 in a small group of patients with Still's disease with atypical lung disease. We sought to characterise features of patients with Still's disease with DRESS compared with drug-tolerant Still's controls. We analysed human leucocyte antigen (HLA) alleles for association to inhibitor-related DHR, including in a small Kawasaki disease (KD) cohort.METHODS: In a case/control study, we collected a multicentre series of patients with Still's disease with features of inhibitor-related DRESS (n=66) and drug-tolerant Still's controls (n=65). We retrospectively analysed clinical data from all Still's subjects and typed 94/131 for HLA. European Still's-DRESS cases were ancestry matched to International Childhood Arthritis Genetics Consortium paediatric Still's cases (n=550) and compared for HLA allele frequencies. HLA association also was analysed using Still's-DRESS cases (n=64) compared with drug-tolerant Still's controls (n=30). KD subjects (n=19) were similarly studied.RESULTS: Still's-DRESS features included eosinophilia (89%), AST-ALT elevation (75%) and non-evanescent rash (95%; 88% involving face). Macrophage activation syndrome during treatment was frequent in Still's-DRESS (64%) versus drug-tolerant Still's (3%; p=1.2*10-14). We found striking enrichment for HLA-DRB1*15 haplotypes in Still's-DRESS cases versus INCHARGE Still's controls (p=7.5*10-13) and versus self-identified, ancestry-matched Still's controls (p=6.3*10-10). In the KD cohort, DRB1*15:01 was present only in those with suspected anakinra reactions.CONCLUSIONS: DRESS-type reactions occur among patients treated with IL-1/IL-6 inhibitors and strongly associate with common HLA-DRB1*15 haplotypes. Consideration of preprescription HLA typing and vigilance for serious reactions to these drugs are warranted.

  View details for DOI 10.1136/annrheumdis-2021-220578

  View details for PubMedID 34789453

• Emergent high fatality lung disease in systemic juvenile arthritis. Annals of the rheumatic diseases Saper, V. E., Chen, G. n., Deutsch, G. H., Guillerman, R. P., Birgmeier, J. n., Jagadeesh, K. n., Canna, S. n., Schulert, G. n., Deterding, R. n., Xu, J. n., Leung, A. N., Bouzoubaa, L. n., Abulaban, K. n., Baszis, K. n., Behrens, E. M., Birmingham, J. n., Casey, A. n., Cidon, M. n., Cron, R. Q., De, A. n., De Benedetti, F. n., Ferguson, I. n., Fishman, M. P., Goodman, S. I., Graham, T. B., Grom, A. A., Haines, K. n., Hazen, M. n., Henderson, L. A., Ho, A. n., Ibarra, M. n., Inman, C. J., Jerath, R. n., Khawaja, K. n., Kingsbury, D. J., Klein-Gitelman, M. n., Lai, K. n., Lapidus, S. n., Lin, C. n., Lin, J. n., Liptzin, D. R., Milojevic, D. n., Mombourquette, J. n., Onel, K. n., Ozen, S. n., Perez, M. n., Phillippi, K. n., Prahalad, S. n., Radhakrishna, S. n., Reinhardt, A. n., Riskalla, M. n., Rosenwasser, N. n., Roth, J. n., Schneider, R. n., Schonenberg-Meinema, D. n., Shenoi, S. n., Smith, J. A., Sönmez, H. E., Stoll, M. L., Towe, C. n., Vargas, S. O., Vehe, R. K., Young, L. R., Yang, J. n., Desai, T. n., Balise, R. n., Lu, Y. n., Tian, L. n., Bejerano, G. n., Davis, M. M., Khatri, P. n., Mellins, E. D. 2019

  Abstract

  To investigate the characteristics and risk factors of a novel parenchymal lung disease (LD), increasingly detected in systemic juvenile idiopathic arthritis (sJIA).In a multicentre retrospective study, 61 cases were investigated using physician-reported clinical information and centralised analyses of radiological, pathological and genetic data.LD was associated with distinctive features, including acute erythematous clubbing and a high frequency of anaphylactic reactions to the interleukin (IL)-6 inhibitor, tocilizumab. Serum ferritin elevation and/or significant lymphopaenia preceded LD detection. The most prevalent chest CT pattern was septal thickening, involving the periphery of multiple lobes ± ground-glass opacities. The predominant pathology (23 of 36) was pulmonary alveolar proteinosis and/or endogenous lipoid pneumonia (PAP/ELP), with atypical features including regional involvement and concomitant vascular changes. Apparent severe delayed drug hypersensitivity occurred in some cases. The 5-year survival was 42%. Whole exome sequencing (20 of 61) did not identify a novel monogenic defect or likely causal PAP-related or macrophage activation syndrome (MAS)-related mutations. Trisomy 21 and young sJIA onset increased LD risk. Exposure to IL-1 and IL-6 inhibitors (46 of 61) was associated with multiple LD features. By several indicators, severity of sJIA was comparable in drug-exposed subjects and published sJIA cohorts. MAS at sJIA onset was increased in the drug-exposed, but was not associated with LD features.A rare, life-threatening lung disease in sJIA is defined by a constellation of unusual clinical characteristics. The pathology, a PAP/ELP variant, suggests macrophage dysfunction. Inhibitor exposure may promote LD, independent of sJIA severity, in a small subset of treated patients. Treatment/prevention strategies are needed.

  View details for DOI 10.1136/annrheumdis-2019-216040

  View details for PubMedID 31562126

• Lung Ultrasound in Children with Systemic Juvenile Idiopathic Arthritis Associated Interstitial Lung Disease. Arthritis care & research Vega-Fernandez, P., Ting, T. V., Mar, D. A., Schapiro, A. H., Deluna, M. D., Saper, V. E., Grom, A. A., Schulert, G. S., Fairchild, R. M. 2022

  Abstract

  OBJECTIVE: Lung disease associated with Systemic Juvenile Idiopathic Arthritis (sJIA-LD) is a potentially life threating complication in children with sJIA. Although high resolution computed tomography (HRCT) is considered the gold standard imaging modality for evaluating interstitial lung disease (ILD), lung ultrasound (LUS) has shown utility for ILD screening in adults with connective tissue diseases (CTD) at lower cost and without utilizing ionizing radiation. The goals of this pilot study were to describe LUS features in children with known SJIA-LD and to assess the feasibility of LUS in this population.METHODS: Children <18years with sJIA-LD and healthy controls were enrolled. LUS acquisition was performed at 14 lung positions. Demographic, clinical, and HRCT data were collected and reviewed. Feasibility was assessed through patient surveys. LUS findings were qualitatively and semi-quantitatively assessed and compared to HRCT findings.RESULTS: LUS was performed in 9 children with sJIA-LD and 6 healthy controls and took 12 minutes on average to perform. LUS findings in sJIA-LD included focal to diffuse pleural irregularity, granularity, and thickening, with associated scattered or coalesced B-lines, and subpleural consolidations. LUS findings appeared to correspond to HRCT findings.CONCLUSION: LUS in sJIA-LD reveals highly conspicuous abnormalities in the pleura and sub-pleura that appear to correlate with peripheral lung findings on HRCT. LUS is a feasible imaging tool in children even from an early age. This study suggests a potential role of LUS in sJIA-LD screening, diagnosis, and/or prognostication.

  View details for DOI 10.1002/acr.24957

  View details for PubMedID 35604884

• Serum proteome analysis of systemic JIA and related lung disease identifies distinct inflammatory programs and biomarkers. Arthritis & rheumatology (Hoboken, N.J.) Chen, G., Deutsch, G. H., Schulert, G., Zheng, H., Jang, S., Trapnell, B., Lee, P., Macaubas, C., Ho, K., Schneider, C., Saper, V. E., de Jesus, A. A., Krasnow, M., Grom, A., Goldbach-Mansky, R., Khatri, P., Mellins, E. D., Canna, S. W. 2022

  Abstract

  OBJECTIVES: Recent observations in systemic Juvenile Idiopathic Arthritis (sJIA) suggest an increasing incidence of high-mortality interstitial lung disease (sJIA-LD) often characterized by a variant of pulmonary alveolar proteinosis (PAP). Co-occurrence of macrophage activation syndrome (MAS) and PAP in sJIA suggested a shared pathology, but sJIA-LD patients also commonly experience features of drug reaction such as atypical rashes and eosinophilia. We sought to investigate immunopathology and identify biomarkers in sJIA, MAS, and sJIA-LD.METHODS: We used SOMAscan to measure >1300 analytes in sera from healthy controls and patients with sJIA, MAS, sJIA-LD and other related diseases. We verified selected findings by ELISA and lung immunostaining. Because the proteome of a sample may reflect multiple states (sJIA, MAS, sJIA-LD), we used regression modeling to identify subsets of altered proteins associated with each state. We tested key findings in a validation cohort.RESULTS: Proteome alterations in active sJIA and MAS overlapped substantially, including known sJIA biomarkers like SAA and S100A9, and novel elevations of heat shock proteins and glycolytic enzymes. IL-18 was elevated in all sJIA groups, particularly MAS and sJIA-LD. We also identified an MAS-independent sJIA-LD signature notable for elevated ICAM5, MMP7, and allergic/eosinophilic chemokines, which have been previously associated with lung damage. Immunohistochemistry localized ICAM5 and MMP7 in sJIA-LD lung. ICAM5's ability to distinguish sJIA-LD from sJIA/MAS was independently validated.CONCLUSION: Serum proteins support an sJIA-to-MAS continuum, help distinguish sJIA, sJIA/MAS, and sJIA-LD and suggest etiologic hypotheses. Select biomarkers, such as ICAM5, could aid in early detection and management of sJIA-LD.

  View details for DOI 10.1002/art.42099

  View details for PubMedID 35189047

• Emergent high fatality lung disease in systemic juvenile arthritis (vol 78, pg 1722, 2019) ANNALS OF THE RHEUMATIC DISEASES Saper, V. E., Chen, G., Deutsch, G. H. 2022; 81 (2)

  View details for DOI 10.1136/annrheumdis-2019-216040corr1

  View details for Web of Science ID 000743668600018

• Effect of Drug Withdrawal on Interleukin-1 or Interleukin-6 Inhibitor Associated Diffuse Lung Disease Saper, V., Prahalad, S., Canna, S., Abdul-Aziz, R., Alvarez, M., Bingham, C., Bader-Meunier, B., Balboni, I., Berard, R., Bolaria, R., Boneparth, A., Casey, A., Cassidy, E., Chang, J. C., Cidon, M., Collins, K., Dickenson, A. M., Espada, G., Fishman, M., Flanagan, E., Hahn, T., Jindal, A. K., Kasapcopur, O., Klein-Gitelman, M., Klouda, T., Kostik, M., Lake, C., Marques, M., Ombrello, M., Onel, K., Phadke, O., Ravelli, A., Reinhardt, A., Robinson, A. D., Rouster-Stevens, K., Saad, N., Schulert, G., Shenoi, S., Stingl, C., Sura, A., Tesher, M., Tibaldi, J., Torok, K., Tsin, C., Vasquez-Canizares, N., Villacis-Nunez, D., Whitehead, B., Wobma, H., Zemel, L., Mellins, E. WILEY. 2021: 3403-3405

  View details for Web of Science ID 000744545206195

• Standardizing Care and Fostering Systemic Autoinflammatory Disease (SAID) Research Through the CARRA Autoinflammatory Disease Network Schulert, G., Cherian, J., Muskardin, T., Twilt, M., Akoghlanian, S., Amarilyo, G., Dissanayake, D., Durrant, K., Ferguson, P., Gutierrez, M., Harel, L., Hausmann, J., Bekenstein, M., Laxer, R., Lenert, A., Li, S., Licameli, G., Lionetti, G., Michelow, I., Moorthy, L., Propst, E., Saper, V., Srinivasalu, H., Stepanovskiy, Y., Thatayatikom, A., Tucker, L., Wright, P., Yildirim-Toruner, C., Dedeoglu, F., Lapidus, S., CARRA Investigators WILEY. 2020: 153–55

  View details for Web of Science ID 000542687800086

• Response to: 'Successful treatment of plasma exchange for refractory systemic juvenile idiopathic arthritis complicated with macrophage activation syndrome and severe lung disease' by Sato et al. Annals of the rheumatic diseases Saper, V. E., Chen, G., Guillerman, R. P., Khatri, P., Cron, R. Q., Mellins, E. D. 2020

  View details for DOI 10.1136/annrheumdis-2020-217426

  View details for PubMedID 32317313

• Drug Reaction and High Fatality Lung Disease in Systemic Onset Juvenile Idiopathic Arthritis (sJIA) Saper, V., Mellins, E., Kwong, B. MOSBY-ELSEVIER. 2020: AB95

  View details for Web of Science ID 000517092700293

• Response to: 'Effectiveness and safety of ruxolitinib for the treatment of refractory systemic idiopathic juvenile arthritis like associated with interstitial lung disease: case report' by Bader-Meunier et al. Annals of the rheumatic diseases Saper, V. E., Chen, G. n., Khatri, P. n., Mellins, E. D. 2020

  View details for DOI 10.1136/annrheumdis-2020-217000

  View details for PubMedID 32054603

• Multiplex Serum Analysis Identifies Potential Biomarkers of Systemic Juvenile Idiopathic Arthritis, Macrophage Activation Syndrome, and Associated Pulmonary Alveolar Proteinosis: Evidence for Independently-regulated Hyperinflammatory and Eosinophilic Inflammation Chen, G., Schulert, G., De Jesus, A., Saper, V., Schneider, C., Trapnell, B., Grom, A. A., Goldbach-Mansky, R., Mellins, E., Khatri, P., Canna, S. WILEY. 2019

  View details for Web of Science ID 000507466901341

• LUNG DISEASE IN SYSTEMIC JIA: AN EMERGING PROBLEM LINKED WITH YOUNG AGE AND ANTI-IL-1/IL-6 Chen, G., Saper, V., Deutsch, G., Guillerman, R. P., Jagadeesh, K., Schulert, G., Canna, S., Lu, Y., Birgmeier, J., Leung, A., Grom, A., Bejerano, G., Davis, M., Khatri, P., Mellins, E., Consortium sJIA-LD Case Reporters BMJ PUBLISHING GROUP. 2019: A57

  View details for DOI 10.1136/annrheumdis-2018-EWRR2019.115

  View details for Web of Science ID 000466415300116

• The 14th International Workshops on Opportunistic Protists (IWOP 14) Cushion, M. T., Limper, A. H., Porollo, A., Saper, V. E., Sinai, A. P., Weiss, L. M. WILEY. 2018: 934–39

  View details for DOI 10.1111/jeu.12631

  View details for Web of Science ID 000451783600018

• The 14th International Workshops on Opportunistic Protists (IWOP 14). The Journal of eukaryotic microbiology Cushion, M. T., Limper, A. H., Porollo, A., Saper, V. E., Sinai, A. P., Weiss, L. M. 2018

  Abstract

  The 14th International Workshops on Opportunistic Protists (IWOP-14) was held August 10-12, 2017 in Cincinnati, OH, USA. The IWOP meetings focus on opportunistic protists (OIs); for example, free-living amoebae, Pneumocystis spp., Cryptosporidium spp., Toxoplasma, the Microsporidia, and kinetoplastid flagellates. The highlights of Pneumocystis spp. research included the reports of primary homothallism for mating; a potential requirement for sexual replication in its life cycle; a new antigen on the surface of small asci; roles for CLRs, Dectin-1, and Mincle in host responses; and identification of MSG families and mechanisms used for surface variation. Studies of Cryptosporidia spp. included comparative genomics, a new cryopreservation method; the role of mucin in attachment and invasion, and epidemiological surveys illustrating species diversity in animals. One of the five identified proteins in the polar tube of Microsporidia, PTP4, was shown to play a role in host infection. Zebrafish were used as a low cost vertebrate animal model for an evaluation of potential anti-toxoplasma drugs. Folk medicine compounds with anti-toxoplasma activity were presented, and reports on the chronic toxoplasma infection provided evidence for increased tractability for the study of this difficult life cycle stage. Escape from the parasitophorus vacuole and cell cycle regulation were the topics of the study in the acute phase.

  View details for PubMedID 29722096

• Altered signaling in systemic juvenile idiopathic arthritis monocytes CLINICAL IMMUNOLOGY Macaubas, C., Wong, E., Zhang, Y., Nguyen, K. D., Lee, J., Milojevic, D., Shenoi, S., Stevens, A. M., Ilowite, N., Saper, V., Lee, T., Mellins, E. D. 2016; 163: 66-74

  Abstract

  Systemic juvenile idiopathic arthritis (sJIA) is characterized by systemic inflammation and arthritis. Monocytes are implicated in sJIA pathogenesis, but their role in disease is unclear. The response of sJIA monocytes to IFN may be dysregulated. We examined intracellular signaling in response to IFN type I (IFNα) and type II (IFNγ) in monocytes during sJIA activity and quiescence, in 2 patient groups. Independent of disease activity, monocytes from Group 1 (collected between 2002 and 2009) showed defective STAT1 phosphorylation downstream of IFNs, and expressed higher transcript levels of SOCS1, an inhibitor of IFN signaling. In the Group 2 (collected between 2011 and 2014), monocytes of patients with recent disease onset were IFNγ hyporesponsive, but in treated, quiescent subjects, monocytes were hyperresponsive to IFNγ. Recent changes in medication in sJIA may alter the IFN hyporesponsiveness. Impaired IFN/pSTAT1 signaling is consistent with skewing of sJIA monocytes away from an M1 phenotype and may contribute to disease pathology.

  View details for DOI 10.1016/j.clim.2015.12.011

  View details for Web of Science ID 000370585600010

  View details for PubMedID 26747737

• Increased local and systemic FGF expression in eosinophilic esophagitis Huang, J., Fuentebella, J., Patel, A., Nguyen, T., Seki, S., Reshamwala, N., Saper, Nguyen, C., Quiros, A., Bass, D., Berquist, W., Kerner, J., Nadeau, K. WILEY-BLACKWELL. 2010: 343

  View details for Web of Science ID 000329462101384

• Study Of Sublingual Immunotherapy In Subjects With Dermatophagoides Farniae And Timothy Grass Allergy Reshamwala, N. R., Song, S. J., Yu, G. P., Swamy, R., Berquist, S. W., Nguyen, T., Hoyt, E. G., Vissamsetti, S., Sivagnanasundaram, A. M., Saper, V. E., Hwang, P. H., Moss, R. B., Nadeau, K. C. MOSBY-ELSEVIER. 2009: S126

  View details for DOI 10.1016/j.jaci.2008.12.467

  View details for Web of Science ID 000263596300494

• CLINICAL AND IMMUNOLOGICAL STUDIES OF CADAVERIC RENAL-TRANSPLANT RECIPIENTS GIVEN TOTAL-LYMPHOID IRRADIATION AND MAINTAINED ON LOW-DOSE PREDNISONE TRANSPLANTATION Saper, V., Chow, D., ENGLEMAN, E. D., Hoppe, R. T., Levin, B., Collins, G., Strober, S. 1988; 45 (3): 540-546

  Abstract

  Twenty-five recipients of cadaveric renal transplants were given total lymphoid irradiation (TLI), perioperative antithymocyte globulin, and low-dose prednisone as the sole maintenance immunosuppressive drug. Nine patients were diabetic, and follow-up was between 19 and 37 months. One-year graft and patient survival was 76% and 87%, respectively, Serious complications included four deaths from cardiovascular disorders, and two deaths from viral infections. Studies of peripheral blood T cell subsets showed a prolonged reduction in the absolute number of helper (Leu-3+) cells, and a rapid recovery of cytotoxic/suppressor (Leu-2+) cells. Analysis of the latter subset, using the monoclonal antibody 9.3, showed that the ratio of suppressor/cytotoxic cells was approximately 10:1. The normal ratio is 1:1. The mean mixed leukocyte reaction remained below 30% of the pre-TLI value for 6 months, and approached 80% at two years. Similar kinetics were observed in the proliferative response to mitogens. The results show that maintenance immunosuppressive drug therapy can be reduced after TLI as compared with conventional drug regimens that use prednisone in combination with cyclosporine and/or azathioprine.

  View details for Web of Science ID A1988M597000008

  View details for PubMedID 3279577

• RENAL-TRANSPLANT PATIENTS TREATED WITH TOTAL LYMPHOID IRRADIATION SHOW SPECIFIC UNRESPONSIVENESS TO DONOR ANTIGENS IN THE MIXED LEUKOCYTE REACTION (MLR) JOURNAL OF IMMUNOLOGY Chow, D., Saper, V., Strober, S. 1987; 138 (11): 3746-3750

  Abstract

  A group of 25 cadaveric renal transplant recipients received total lymphoid irradiation (TLI) before transplantation, rabbit anti-thymocyte globulin on alternate days for 10 days after transplantation, and low dose prednisone (5 to 10 mg/day) as the sole maintenance immunosuppressive therapy. Allograft function and the mixed leukocyte reaction (MLR) were monitored serially. After 18 to 30 mo, nine patients were selected on the basis of a return of the MLR such that the mean stimulation index to a panel of normal stimulator cells was greater than or equal to 5, a stable serum creatinine level which was less than or equal to 2 mg/dl, and a history of no more than one rejection episode. The MLR of these patients' post-transplant peripheral blood mononuclear leukocytes (PBML) against cryopreserved donor cells was compared with that against cryopreserved normal third-party cells. In control experiments, the MLR of cryopreserved pre-TLI recipient PBML or fresh normal PBML were tested against the same panel of donor and third-party stimulator cells. Seven of the nine recipients showed a pattern of specific unresponsiveness to the donor cells more than 18 mo after transplantation. Preliminary attempts to identify antigen specific suppressor cells were unsuccessful. The pattern of unresponsiveness may indicate a state of specific immune tolerance to the allogeneic graft.

  View details for Web of Science ID A1987H389200028

  View details for PubMedID 2953791

• USE OF THE ACOUSTIC REFLECTOMETER (AR) IN ATOPIC PATIENTS SAPER, V. E., FRICK, O. L. AMER COLL ALLERGY ASTHMA IMMUNOLOGY. 1985: 352

  View details for Web of Science ID A1985AFN6900074

• BRONCHOSPASTIC RESPONSES TO AEROSOLIZED METABISULFITE IN ASTHMATIC SUBJECTS JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY SAPER 1985; 76 (1): 128-129

  View details for DOI 10.1016/0091-6749(85)90817-6

  View details for Web of Science ID A1985AMV8400020