The Department of Microbiology at the College of Medicine, Al-Nahrain University, discussed the PhD dissertation of the student Ahmed Hilal Kamel, titled: “Association of Protein Tyrosine Phosphatase Receptor Type C, Interleukins-33 and 6 with Response to TNF Inhibitor in Rheumatoid Arthritis Patients.” The study aimed to evaluate the association between the genetic polymorphisms of PTPRC (rs10919563), IL-33 (rs16924159), and IL-6 (rs1800795) with the susceptibility to rheumatoid arthritis (RA) and the response to TNF inhibitor therapy. It also sought to compare the serum levels of these proteins between RA patients and healthy individuals, as well as to investigate their expression relationship with treatment response. The study included 100 RA patients (50 responders and 50 non-responders to therapy) and 100 age- and sex-matched healthy controls. Genotyping of the studied variants was performed using quantitative PCR (TaqMan assay), and serum levels of PTPRC, IL-33, and IL-6 were measured using the ELISA technique. Clinical assessment was conducted using the Clinical Disease Activity Index (CDAI), along with measurement of serological markers including Rheumatoid Factor (RF), Anti-Cyclic Citrullinated Peptide (Anti-CCP), and C-Reactive Protein (CRP). Statistical analyses were performed to compare genotype and allele distributions, assess their association with disease susceptibility and treatment response, and evaluate diagnostic performance using ROC curves. The results demonstrated significantly higher serum concentrations of PTPRC, IL-33, and IL-6 in RA patients compared to healthy controls (p<0.001), with even higher levels among non-responders than responders (p<0.001), indicating their role in disease activity and treatment resistance. The AA genotype of PTPRC rs10919563 (p=0.027) and the A allele (p=0.047) were more prevalent among non-responders, with no significant association with disease susceptibility. Similarly, the AA genotype of IL-33 rs16924159 (p=0.040) was significantly associated with non-response to TNF inhibitors, but not with disease susceptibility. In contrast, the IL-6 rs1800795 polymorphism showed a dual significance: the C allele was more frequent in RA patients compared to controls (p=0.022), suggesting its association with disease susceptibility, while the CC genotype (p=0.019) and C allele (p=0.009) were also more frequent among non-responders, indicating a strong association with treatment resistance. Diagnostic analysis revealed that IL-6 was the most accurate biomarker (AUC=0.999,>), followed by PTPRC (AUC=0.979) and IL-33 (AUC=0.810).
These findings suggest that PTPRC and IL-33 polymorphisms are significantly associated with non-response to TNF inhibitor therapy, while IL-6 polymorphism is linked to both disease susceptibility and therapeutic resistance. Elevated serum levels of these three proteins are associated with RA diagnosis and poor treatment response. The study supports the potential of IL-6, along with PTPRC and IL-33, as valuable genetic and serological biomarkers for guiding personalized and targeted therapeutic strategies in RA patients. The examining committee consisted of: Prof. Dr. Nidal Abdul-Muhaimen Mohammed – Chair Prof. Dr. Shahla Mahdi Saleh – Member Prof. Dr. Faiq Aisho Koryal – Member Prof. Dr. Haider Ahmed Shumran – Member Prof. Dr. Haider Faisal Ghazi – Member Prof. Dr. Ahmed Abdul-Hassan Abbas – Member and Supervisor
The dissertation was accepted with a grade of Excellent. 
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