HYPER IGM SYNDROME TYPE 1 CARRIER WITH RECURRENT INFECTIONS; MORE THAN JUST A CARRIER.

Abstract

Introduction CD40 ligand (CD40L) deficiency is an X-linked hyper-IgM syndrome that presents with defects in humoral and cellular immunity, resulting in severe bacterial and opportunistic infections, as well as autoimmunity and malignancy. Female carriers of CD40L deficiency should be asymptomatic and have normal immunoglobulin levels. Case Description A 38-year-old female CD40L deficiency carrier presented with CMV hepatitis, several hospitalizations for pyelonephritis and recurrent upper respiratory infections. She demonstrated elevated IgM, normal IgG with an abnormal polysaccharide response. She also had low B cells with a normal proportion of B cell subsets. Lymphocyte stimulation showed a low response to Tetanus Toxoid and Candida albicans antigen. Her mutation occurred at a CD40L splice site that results in the utilization of several alternative splice sites and the expression of a wild-type protein of unknown function. Her T-cell studies demonstrated 56% CD40L expression and 57% binding to the soluble CD40L receptor making extreme lyonization unlikely. Whole exome sequencing was performed. She was started on with immunoglobulin replacement and demonstrated clinical improvement. Discussion This is the first known case describing a symptomatic carrier of CD40L deficiency without evidence of skewed X-linked inactivation. Although CD40L deficiency carriers are typically thought to be asymptomatic our case demonstrates the need for a high index of suspicion and continued thoughtful evaluation in patients with atypical presentations.