Background/Purpose: Human inborn errors of immunity are caused by monogenic germline mutations characterized by Immunodeficiency like features with increase susceptibility to infection as well as concomitant diversity of autoimmune, autoinflammatory manifestations. We aim to describe the phenotype and genotype features of patients with genetically confirmed autoinflammatory disease (AID) associated with immunodeficiency.

Methods: Data of 22 patients with confirmed monogenic AID and immunodeficiency features were retrospectively collected. Medical records were reviewed for demographic, family history, clinical and genetic data. Sequencing analysis was done in all included patients.

Results: Out of 125 patients with AID, 22 patients (13 female) have been evaluated since 2005. Median age of disease onset 17 months (IQR: 6-36) and median age of diagnosis 4.5 years (IQR: 3-8.5). Parental consanguinity rate was (77%). Patients had variations in the following genes: RNF31, OTULIN, WDR1, ISG15, STAT1, TNFAIP3, SOCS1, NLRP12, ADA2, ILRA17, ZNFX1, STING, IFIH1, DNASE2. Among the 17 detected variants, (61%) identified as novel. Notably, genetic variations associated with type I Interferon and NF-KB pathways were the most frequent AID. The main clinical features were fever (100%), cutaneous (72%), gastrointestinal (68%), neurology (63%), MSK (59%), and pulmonary (45%). Immunodeficiency features included recurrent infections (68%) mostly viral, hypogammaglobinemia (77%), and abnormal lymphocyte markers (63%). Two patients had mycobacterial infection. Immunoglobulin therapy and prophylactic antibiotics were frequently administered. More than half of the patients required steroids and immunomodulatory agents. BMT done in 1 patient. The mean accrual damage was 6.6+3.4. There were 2 deaths reported secondary to infections.

Conclusion: Immunodeficiency manifestations are frequently detected in interferon and NF-KB monogenic AID. The concomitant use of immunoglobulin and prophylactic antimicrobial with immunosuppressive therapy played a fundamental balance. We have identified rare and novel genetic variants which probably contributed to the increased incidence of immunodeficiency in AID.  

« Back to ACR Convergence 2024

ACR Meeting Abstracts - https://acrabstracts.org/abstract/immunodeficiency-related-monogenic-autoinflammatory-diseases-expanding-spectrum-of-immunodysregulation-disorders/