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FCGR2A-131H/H is under-represented amongst patients with primary immunodeficiencies

Flewitt, E. W. D.; Charlesworth, J. E. G.; Patel, S. Y.; Hargreaves, C. E.

2023-10-13 allergy and immunology
10.1101/2023.10.12.23296440 medRxiv
Show abstract

The Fc{gamma} receptors (Fc{gamma}Rs) act as modulators of the immune system and have previously been shown to play a role in immune disorders such as systemic lupus erythematosus and immune thrombocytopenic purpura. Thus far, their role in primary immunodeficiencies (PID), including common variable immunodeficiency disorders (CVID), has not been studied. In this paper we explored whether there is an association between the following single nucleotide polymorphisms (SNPs) and CVID: FCGR2A H131R (rs1801274), FCGR2B I232T (rs1050501), and FCGR3A F158V (rs396991). We compared the genotypes of a cohort of 83 patients with PID, including 56 with CVID, against controls. We found a significant difference between our mixed PID cohort and controls at the FCGR2A H131R SNP (X2 =7.884, p=0.019). There was not a significant difference at either of the other SNPs studied. Further, we examined the effect of FCGR SNPs on the incidence of the most common CVID complications within our cohort: anaemias, organ-specific autoimmunity, bronchiectasis, splenomegaly, granulomata, and cytopenias. We found no significant association between SNPs and the development of these complications. In summary, we have shown that there is a link between the FCGR2A H131R SNP and the development of a PID.

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