Longitudinal Immune Profiling of T Cell Exhaustion During IL-17A Blockade in a Patient With HLA-B27-negative Spondyloarthritis and Sjögren’s Syndrome: A Case Report

Background/Aim: Coexisting Sjögren’s syndrome (SS) and human leukocyte antigen-B27 (HLA-B27)-negative ankylosing spondylitis (AS) is rare and therapeutically challenging. In patients with prior Stevens-Johnson syndrome (SJS), non-steroidal anti-inflammatory drugs (NSAIDs) are contraindicated and tumor necrosis factor (TNF) inhibitors may be insufficient. Interleukin-17A (IL-17A) blockade with secukinumab offers an alternative, though its long-term effects on T cell exhaustion and regulation remain unclear. This report examines immune exhaustion and regulatory dynamics during IL-17A inhibition in a complex autoimmune case. Case Report: A 52-year-old man with SJS, SS, and HLA-B27-negative AS switched to secukinumab after inadequate TNF inhibition. Flow cytometry over five years (2020, 2023, 2025) tracked early therapy, steroid tapering, and long-term stability. Initial immune profiling revealed expanded effector T cells [Fas cell surface death receptor (Fas)⁺, programmed death protein 1 (PD-1)⁺, T-cell immunoglobulin and mucin-domain containing-3 (Tim-3)⁺] and reduced regulatory subsets. Over time, as disease activity improved, exhaustion markers declined and regulatory T cell (Treg) populations partially recovered. By 2025, the patient maintained low disease activity with minimal steroid exposure. Laboratory data confirmed remission [C-reactive protein (CRP) 0.10 mg/dl, erythrocyte sedimentation rate (ESR) 2 mm/h], while patient-reported indices [Bath ankylosing spondylitis disease activity index (BASDAI) 4.1, ankylosing spondylitis disease activity score using C-reactive protein (ASDAS-CRP) 2.0] reflected stable low-to-moderate disease activity. Naïve T cells continued to show intermittent PD-1 and killer cell lectin-like receptor G1 (KLRG1) expression, suggesting persistent low-level immune adaptation. Conclusion: This case shows phased immune rebalancing under long-term IL-17A blockade. Serial monitoring revealed dynamic exhaustion marker changes and partial regulatory recovery linked to clinical improvement, underscoring the value of longitudinal immune profiling for personalized management of complex autoimmune syndromes.