Multiple autoimmune syndrome: Clinical, immunological and genotypic characterization

Area of Science:

• Immunology and Genetics
• Autoimmune Disease Research
• Clinical Medicine

Background:

• Shared subphenotypes across autoimmune diseases (AIDs) suggest a common physiopathology, termed autoimmune tautology.
• Multiple Autoimmune Syndrome (MAS), defined as the presence of three or more AIDs in one individual, highlights that polyautoimmunity is more than a mere coincidence.

Purpose of the Study:

• To characterize and compare patients with monoautoimmunity versus MAS.
• To investigate whether the clustering of AIDs influences disease severity, autoantibody expression, or genetic polymorphisms that could serve as markers for polyautoimmunity.

Main Methods:

• A cohort of 343 adult patients with AIDs was analyzed, with MAS defined as the presence of three or more AIDs.
• Clinical and immunological data were collected from medical records.
• Genotyping for HLA-DRB1 and PTPN22 (rs2476601) polymorphisms was performed using PCR-SSP and TaqMan Real Time PCR, respectively. Statistical analyses included Chi-Square, Fisher's exact tests, and logistic regression to calculate odds ratios (OR) and 95% confidence intervals.

Main Results:

• Elevated frequencies of HLA-DRB1*03 were observed in the overall study cohort and in monoautoimmune SLE and SjS patients compared to controls.
• MAS patients exhibited significantly higher rates of neuropsychiatric lupus (NPSLE), subacute cutaneous lesions, muscle/tendon involvement, hematological issues, and Raynaud's phenomenon.
• Specific HLA-DRB1 alleles (e.g., *11, *13, *14) and PTPN22 polymorphisms showed differential frequencies associated with monoautoimmunity, MAS, and specific clinical manifestations, with anti-U1RNP frequency being higher in MAS.

Conclusions:

• The coexistence of multiple AIDs (MAS) is associated with a more severe disease course.
• Established genetic risk and protective factors were confirmed, with HLA-DRB1*14 suggested as a novel protective factor.
• HLA-DRB1*07 and anti-U1RNP may serve as markers for mono- and polyautoimmunity, respectively, while HLA-DRB1*13 could predict vascular risk in MAS patients. PTPN22 (rs2476601) may be linked to less severe disease.