Muge Kalaycioglu

All Publications

• Common connective tissue disorder and anti-cytokine autoantibodies are enriched in idiopathic multicentric castleman disease patients. Frontiers in immunology Feng, A., Gonzalez, M. V., Kalaycioglu, M., Yin, X., Mumau, M., Shyamsundar, S., Bustamante, M. S., Chang, S. E., Dhingra, S., Dodig-Crnkovic, T., Schwenk, J. M., Garg, T., Yoshizaki, K., van Rhee, F., Fajgenbaum, D. C., Utz, P. J. 2025; 16: 1528465

  Abstract

  Idiopathic Multicentric Castleman Disease (iMCD) is a polyclonal lymphoproliferative disorder involving cytokine storms that can lead to organ failure and death. The cause of iMCD is unknown, but some clinical evidence suggests an autoimmune etiology. For example, connective tissue disorders (CTDs) and iMCD share many clinical features, and autoantibodies have been anecdotally reported in individual iMCD patients. This study investigates whether common autoantibodies are shared across iMCD patients.We assembled custom bead-based protein arrays consisting of 52 autoantigens traditionally associated with CTDs and 38 full-length cytokines and screened serum samples from 101 iMCD patients for IgG autoantibodies. We also screened samples with a 1,103-plex array of recombinant human protein fragments to identify additional autoantibody targets. Finally, we performed receptor blocking assays on select samples with anti-cytokine autoantibodies (ACAs) identified by array.We found that an increased proportion of iMCD patients (47%) tested positive for at least one CTD-associated autoantibody compared to healthy controls (HC) (17%). Commonly detected CTD-associated autoantibodies were associated with myositis and overlap syndromes as well as systemic lupus erythematosus (SLE) and Sjögren's Syndrome (SS). ACAs were also detected in a greater proportion of iMCD patients (38%) compared to HC (10%), while the protein fragment array identified a variety of other autoantibody targets. One iMCD sample tested positive for receptor blocking against interferon-ω (IFNω).IgG autoantibodies binding autoantigens associated with common CTDs and cytokines are elevated in iMCD patients compared to HC, suggesting that autoimmunity may be involved in iMCD pathogenesis.

  View details for DOI 10.3389/fimmu.2025.1528465

  View details for PubMedID 40181993

  View details for PubMedCentralID PMC11966032

• Unveiling the proteome-wide autoreactome enables enhanced evaluation of emerging CAR-T therapies in autoimmunity. The Journal of clinical investigation Bodansky, A., Yu, D. J., Rallistan, A. N., Kalaycioglu, M., Boonyaratanakornkit, J., Green, D. J., Gauthier, J., Turtle, C. J., Zorn, K. C., O'Donovan, B., Mandel-Brehm, C., Asaki, J., Kortbawi, H., Kung, A. F., Rackaityte, E., Wang, C. Y., Saxena, A., de Dios, K., Masi, G., Nowak, R. J., O'Connor, K. C., Li, H., Diaz, V. E., Saloner, R., Casaletto, K. B., Gontrum, E. Q., Chan, B. J., Kramer, J. H., Wilson, M. R., Utz, P. J., Hill, J. A., Jackson, S. W., Anderson, M. S., DeRisi, J. L. 2024

  Abstract

  Given the global surge in autoimmune diseases, it is critical to evaluate emerging therapeutic interventions. Despite numerous new targeted immunomodulatory therapies, comprehensive approaches to apply and evaluate the effects of these treatments longitudinally are lacking. Here, we leveraged advances in programmable-phage immunoprecipitation (PhIP-Seq) methodology to explore the modulation, or lack thereof, of autoantibody profiles, proteome-wide, in both health and disease. Using a custom set of over 730,000 human derived peptides, we demonstrated that each individual, regardless of disease state, possesses a distinct and complex constellation of autoreactive antibodies. For each individual, the set of resulting autoreactivites constituted a unique immunological fingerprint, or "autoreactome," that was remarkably stable over years. Using the autoreactome as a primary output, we evaluated the relative effectiveness of various immunomodulatory therapies in altering autoantibody repertoires. We found that therapies targeting B-Cell Maturation Antigen (BCMA) profoundly altered an individual's autoreactome, while anti-CD19 and CD20 therapies had minimal effects. These data both confirm that the autoreactome is comprised of autoantibodies secreted by plasma cells, and strongly suggest that BCMA or other plasma cell targeting therapies may be highly effective in treating currently refractory autoantibody mediated diseases.

  View details for DOI 10.1172/JCI180012

  View details for PubMedID 38753445