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

The Fcγ receptors (FcγRs) 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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement SYP is funded by the Oxford NIHR Biomedical Research Centre, EWDF was funded by the University of Oxford, Final Honours School. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical approval covering our use of patient samples and information was granted by the South Central Research Ethics Committee (NHS Health Research Authority, 12/SC/0044). Ethical approval for work using healthy controls was granted to the Oxford Gastrointestinal Illness Biobank, through the University of Oxford, Nuffield Department of Medicine (16/YH/0247). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data that support the findings of this study are available from the corresponding author upon reasonable request. * CMC : chronic mucocutaneous candidiasis CVID : common variable immunodeficiency disorder F : phenylalanine FCGR : Fc gamma receptor H : histidine HWE : Hardy-Weinberg equilibrium I : isoleucine ITP : immune thrombocytopenia purpura PCR : polymerase chain reaction PID : primary immunodeficiencies R : arginine SLE : systemic lupus erythematosus SNP : single nucleotide polymorphism T : threonine V : valine