A Case Report of Hyper-IgM Syndrome Patient with Normal Serum IgA Level

Case Report

Austin J Clin Immunol. 2023; 9(2): 1057.

A Case Report of Hyper-IgM Syndrome Patient with Normal Serum IgA Level

Amer Khojah1*; Lauren Gunderman2,3; Mohammad Binhussein1; Ameera Bukhari4; Imad Khojah5

1College of Medicine, Umm Al-Qura University, Saudi Arabia

2Division of Allergy and Immunology, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, USA

3Northwestern University Feinberg School of Medicine, Chicago, IL, USA

4College of Science, Taif University, Saudi Arabia

5Faculty of Medicine, King Abdulaziz University, Saudi Arabia

*Corresponding author: Amer Khojah, MD Pediatrics Department, College of Medicine, Umm Al-Qura University, Saudi Arabia, PO Box 715, Al Abdeyah, Makkah, 24381, Saudi Arabia. Phone: +966 56 504 4998 Email: amkhojah@uqu.edu.sa

Received: May 30, 2023 Accepted: June 20, 2023 Published: June 27, 2023

Abstract

Hyper IgM syndromes are a group of disorders characterized by defective T and B cell interactions resulting in the lack of Immunoglobulin class switching. The most common hyper IgM syndrome is CD40 ligand (CD40L) deficiency. Patients with CD40L deficiency present with recurrent infection, neutropenia, and autoimmunity. These patients typically have absent serum IgA and IgG due to the class switch defect. Here we present a case of CD40L deficiency who presented with oral ulcers, failure to thrive, and recurrent fever. His laboratory evaluation was notable for intermittent neutropenia, elevated IgM (397mg/dl), normal IgA (78mg/dl) and low IgG (51mg/dl). Antibody responses to tetanus and measles were undetectable despite full vaccination. Whole exome sequencing showed a likely pathologic variant in CD40LG (c.674 T>C, p.L225S). This case highlights the importance of considering the diagnosis of hyper IgM syndrome in the appropriate clinical setting, even if the patient has a normal serum IgA level.

Keywords: Hyper IgM syndromes; IgA; CD40LG; Pneumatosis intestinalis

Abbreviations: CD40L: CD40 ligand; XHIGM: X-linked Hyper-IgM Syndrome; PJP: Pneumocystis Jiroveci Pneumonia; GI: Gastrointestinal; CRP: C - Reactive Protein; Hib: Haemophilus Influenzae Type b; IVIG: Intravenous Immunoglobulin; NK: Natural Killer, G-CSF Therapy: Granulocyte Colony Stimulating Factor Therapy; COVID-19: Corona Virus Disease of 2019; HSCT: Hematopoietic Stem Cell Transplantation

Introduction

Hyper IgM syndromes are a group of inborn error of immunity disorders that are characterized by the lack of Immunoglobulin class switching due to defective T and B cell interactions [1]. Hyper-IgM syndrome patients typically have markedly reduced serum concentrations of IgG and IgA with normal to elevated levels of IgM and normal B cell count [1,2]. The most common hyper IgM syndrome is CD40 ligand (CD40L) deficiency which is due to mutation in the CD40LG gene located at the X chromosome (Xq26.3-27) [3]. The estimated incidence of CD40L deficiency, also known as X-linked hyper-IgM syndrome (XHIGM), in the United States is around 1:1,030,000 live births [4]. CD40L is expressed on CD4+ T cells upon activation and interacts with CD40, which is expressed constitutively by B cells [5]. This interaction leads to B cell class switching and somatic hypermutation (Figure 1) [5]. Patients with XHIGM typically present with respiratory tract infections, including Pneumocystis Jiroveci Pneumonia (PJP) in infancy [3,4,6]. In addition to typical bacterial infections, XHIGM patients are susceptible to opportunistic infections in addition to PJP, such as Cryptococcus, Candida, Histoplasma, Leishmania, and Cryptosporidium, which may lead to sclerosing cholangitis [4,7]. Other complications include neutropenia, autoimmunity, liver disease, and malignancy [6]. The immunology evaluation of XHIGM patients typically reveals normal to elevated levels of IgM with reduced or absent serum concentrations of IgG and IgA due to the class switch defect [2]. Here we report a case of XHIGM in a young body with oral ulcers, failure to thrive, recurrent fever, neutropenia, and normal serum IgA level. Although hyper-IgM syndromes classically present with absent serum IgA and IgG, the diagnosis should not be excluded in a patient with normal serum IgA level when suspicion for the diagnosis is high.

Citation: Khojah A, Gunderman L, Binhussein M, Bukhari A, Khojah I. A Case Report of Hyper-IgM Syndrome Patient with Normal Serum IgA Level. Austin J Clin Immunol. 2023; 9(2): 1057.