Consensus Middle East and North Africa Registry on Inborn Errors of Immunity

Background: Inborn errors of immunity (IEIs) are a heterogeneous group of genetic defects of immunity, which cause high rates of morbidity and mortality mainly among children due to infectious and non-infectious complications. The IEI burden has been critically underestimated in countries from middle- and low-income regions and the majority of patients with IEI in these regions lack a molecular diagnosis. Methods: We analyzed the clinical, immunologic, and genetic data of IEI patients from 22 countries in the Middle East and North Africa (MENA) region. The data was collected from national registries and diverse databases such as the Asian Pacific Society for Immunodeficiencies (APSID) registry, African Society for Immunodeficiencies (ASID) registry, Jeffrey Modell Foundation (JMF) registry, J Project centers, and International Consortium on Immune Deficiency (ICID) centers. Results: We identified 17,120 patients with IEI, among which females represented 39.4%. Parental consanguinity was present in 60.5% of cases and 27.3% of the patients were from families with a confirmed previous family history of IEI. The median age of patients at the onset of disease was 36 months and the median delay in diagnosis was 41 months. The rate of registered IEI patients ranges between 0.02 and 7.58 per 100,000 population, and the lowest rates were in countries with the highest rates of disability-adjusted life years (DALY) and death rates for children. Predominantly antibody deficiencies were the most frequent IEI entities diagnosed in 41.2% of the cohort. Among 5871 patients genetically evaluated, the diagnostic yield was 83% with the majority (65.2%) having autosomal recessive defects. The mortality rate was the highest in patients with non-syndromic combined immunodeficiency (51.7%, median age: 3.5 years) and particularly in patients with mutations in specific genes associated with this phenotype (RFXANK, RAG1, and IL2RG). Conclusions: This comprehensive registry highlights the importance of a detailed investigation of IEI patients in the MENA region. The high yield of genetic diagnosis of IEI in this region has important implications for prevention, prognosis, treatment, and resource allocation

Erosive arthritis and anti-cyclic citrullinated peptide antibodies in systemic sclerosis

Background: The frequency and characteristics of erosive arthritis in systemic sclerosis (SSc) remains unclear. The aim of the study was to determine the prevalence and characteristics of erosive arthritis and to define the role of anti-CCP antibodies in the differential diagnosis of joint involvement in SSc. Methods: One hundred and fifty patients who met the 1980 American College of Rheumatology (ACR) criteria and/or Leroy and Medsger criteria for SSc were assessed. Results: Among the 150 SSc patients, 139 were women. Their median age was 45.12 ± 13.59 years and disease duration ( first non-Raynaud symptom) of 9.7 years. Of these patients, 5 patients were classified as having limited SSc, 103 as limited cutaneous SSc and 42 as diffuse cutaneous SSc. Joint involvement was characterized as arthralgia in 95 (63%) patients, arthritis in 60 (40%) patients, erosive arthritis in 21 (14%) and systemic sclerosis (SSc)-rheumatoid arthritis (RA) overlap syndrome in 7 patients. The prevalence of diffuse cutaneous involvement (50%) (P = 0.01), digital ulcers (81%) (P = 0.009), interstitial lung disease (81%) (P = 0.009) and anti-topoisomerase I antibodies (P = 0.01) was higher in patients with erosive arthritis. Anti-CCP antibodies were found in 14 of the 150 (9.4%) cases. A statistically significant association between the presence of anti-CCP antibodies and the presence of arthritis (P = 0.01), erosive arthritis (P = 0.01) and SSc-RA overlap syndrome (P < 0.05) was noted. High titers of anti-CCP antibodies were found in patients with SSc-RA overlap syndrome. Conclusion: Erosive arthritis is not rare in SSc, and it might be a marker of severe disease. Anti-CCP antibodies can be present in patients with SSc, and high titers of anti-CCP antibodies may be indicative of SSc-RA overlap syndrome