The Integrin Signature of Ankylosing Spondylitis: Divergent Regulation of CD29 and CD49b in HLA-B27-Positive Cohorts in Iraqi Patients

Abstract

Background & Objective: Ankylosing spondylitis (AS) is a systemic inflammatory disorder where the HLA-B27 allele significantly influences disease severity. This study evaluated the molecular profiles of integrins CD29 and CD49b in peripheral blood mononuclear cells (PBMCs) to identify potential biomarkers associated with HLA-B27 status. Methods: In this cross-sectional study of an Iraqi cohort, 130 participants were recruited: 50 HLA-B27-positive (HLA+) radiographic AS patients, 50 HLA-B27-negative (HLA−) radiographic AS patients, and 30 healthy controls. Transcriptomic and proteomic expressions of CD29 and CD49b were quantified using qPCR and flow cytometry (mean fluorescence intensity, MFI). Hematological and biochemical profiles were also assessed. Results: CD29 mRNA was significantly upregulated in both patient groups, with a more pronounced median elevation in the HLA+ group (11-fold; P < 0.0001) than in the HLA− group (3-fold; P < 0.001). Surface CD29 protein significantly increased only in the HLA+ cohort (mean MFI approximately 3000; P < 0.0001). Conversely, CD49b mRNA was substantially suppressed, particularly in the HLA+ group (P < 0.0001). Correspondingly, a marked reduction in CD49b surface protein occurred in the HLA+ cohort (mean MFI approximately 300; P < 0.0001), whereas the HLA− group remained statistically comparable to controls. Additionally, the HLA− phenotype was characterized by significant granulocytosis (85%–90%) and more pronounced elevations in urea and ALT levels. Conclusion: These findings suggest a divergent regulation of CD29 and CD49b integrins associated with HLA-B27 status in Iraqi AS patients. While these integrins may serve as molecular indicators for disease stratification, longitudinal validation is required to confirm their clinical utility as diagnostic or therapeutic targets.