Autoimmune Regulator Gene Polymorphisms in Egyptian Systemic Lupus Erythematosus Patients: Preliminary Results

Abstract

Background. Systemic lupus erythematosus (SLE) is a systemic autoimmune disease. The autoimmune regulator (AIRE) is a master regulator of self-tolerance development. AIRE mutations lead to the development of autoimmune polyglandular syndrome type 1 while AIRE polymorphisms have been linked to organ-specific autoimmunity. The study is aimed at addressing the association between AIRE polymorphisms, rs2075876 (G > A) and rs760426 (A > G), and SLE susceptibility and expression in Egyptian patients. Methods. Ninety-nine patients were included. One hundred and ten, and 123 control subjects were genotyped for rs2075876 and rs760426, respectively. Lupus severity was assessed using the Lupus Severity of Disease Index and Lupus Severity Index (LSI). Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) damage index was considered. Genotyping was done using StepOne Real-Time PCR. Results. AIRE rs760426 GG was more frequent in the patients under the genotype level (14.1% vs. 4.9%, p = 0.032 ) and recessive model (14.1% vs. 4.9%, p = 0.017 , OR = 3.2 (1.2-8.7)). Musculoskeletal involvement and nephritis were associated with AIRE rs2075876 under the dominant (97.9% vs. 80.8%, p = 0.009 , OR = 11 (1.3-89.2)) and recessive models (100% vs. 69.3%, p = 0.032 ), respectively; and both were linked to AIRE rs2075876 at the allelic level: 98.3% vs. 85%, p = 0.005 , OR = 10.1 (1.3-76.6) and 82.8% vs. 68.6, p = 0.041 , OR = 2.2 (1-4.7), respectively. Patients with AIRE rs2075876 A alleles had a higher damage index ( 1 ± 1.3 vs. 0.6 ± 1.1, p = 0.045 ) while the LSI was greater in patients with AIRE rs2075876 (8.5 ± 0.5 vs. 7.8 ± 1.3, p = 0.002 ) and rs760426 (8.6 ± 11 vs. 7.8 ± 1.2, p = 0.031 ) under the recessive models. Conclusion. AIRE rs760426 could share in SLE susceptibility while AIRE rs2075876 could influence the disease expression and burden in Egyptian patients.

Immunogenetic Relationship of HLA-G 14 bp Insertion/Deletion Polymorphism and Toll-Like Receptor 9 with Systemic Lupus Erythematosus in Egyptian Patients: A Case-Control Study

“…This comes consistent with previous studies carried out among Egyptian patients where musculoskeletal (arthritis), mucocutaneous (rash), and LN were the most common phenotypes. 4,6 The present study demonstrated a significant association between HLA-G 3ˊUTR polymorphisms (HLA-G ins/del rs371194629), previously suggested to have functional significance, 17 with SLE susceptibility for the first time among Egyptian patients. A significant over-presentation of the HLA-G ins allele has been observed in SLE patients versus healthy subjects with a significant difference in the frequency of ins/ins genotype among both groups (P < 0.001, OR = 11.79) highlighting it as a potential risk factor for SLE development among those patients.…”

“…This comes consistent with previous studies carried out among Egyptian patients where musculoskeletal (arthritis), mucocutaneous (rash), and LN were the most common phenotypes. 4 , 6 …”

“…3 Among Egyptian patients, different genetic polymorphisms have been studied and found to be associated with SLE as polymorphisms in the gene coding for the autoimmune regulator (AIRE), type I interferon (IFN) pathway, interleukin 27, programmed cell death 1 (PD1), tumor necrosis factor (TNF-α) and IFN-γ. [4][5][6][7][8] However, the role of the human leukocyte antigen-G (HLA-G) gene has not been addressed before among Egyptian patients.…”