Novel Presentation of Major Histocompatibility Complex Class II Deficiency with Hemophagocytic Lymphohistiocytosis.

Purpose: Major histocompatibility complex (MHC) class II deficiency is one of the combined immune deficiency disorders caused by defects in the MHC class II regulatory genes leading to abnormal T cells development and function. Therefore, patients mainly present with increased susceptibility to infections, diarrhea, and failure to thrive. In this report, we present one MHC class II deficient patient with a novel presentation with Hemophagocytic Lymphohistiocytosis (HLH).

The Middle East and North Africa Diagnosis and Management Guidelines for Inborn Errors of Immunity.

Human inborn errors of immunity (IEI) are a group of 485 distinct genetic disorders affecting children and adults. Signs and symptoms of IEI are heterogeneous, and accurate diagnosis can be challenging and depends on the available human expertise and laboratory resources. The Middle East and North Africa (MENA) region has an increased prevalence of IEI because of the high rate of consanguinity with a predominance of autosomal recessive disorders.

DOCK8 Deficiency Presenting as an IPEX-Like Disorder.

Purpose: The dedicator of cytokinesis 8 (DOCK8) deficiency is an autosomal recessive-combined immunodeficiency whose clinical spectra include recurrent infections, autoimmunity, malignancies, elevated serum IgE, eczema, and food allergies. Here, we report on patients with loss of function DOCK8 mutations with profound immune dysregulation suggestive of an immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX)-like disorder.

Methods: Immunophenotyping of lymphocyte subpopulations and analysis of DOCK8 protein expression were evaluated by flow cytometry.

Exaggerated follicular helper T-cell responses in patients with LRBA deficiency caused by failure of CTLA4-mediated regulation.

Background: LPS-responsive beige-like anchor protein (LRBA) and cytotoxic T lymphocyte-associated antigen 4 (CTLA4) deficiencies give rise to overlapping phenotypes of immune dysregulation and autoimmunity, with dramatically increased frequencies of circulating follicular helper T (cT) cells.

Objective: We sought to determine the mechanisms of cT cell dysregulation in patients with LRBA deficiency and the utility of monitoring cT cells as a correlate of clinical response to CTLA4-Ig therapy.

Methods: cT cells and other lymphocyte subpopulations were characterized.

T Regulatory Cell Biology in Health and Disease.

Regulatory T (Treg) cells that express the transcription factor forkhead box protein P3 (FOXP3) play an essential role in enforcing immune tolerance to self tissues, regulating host-commensal flora interaction, and facilitating tissue repair. Their deficiency and/or dysfunction trigger unbridled autoimmunity and inflammation. A growing number of monogenic defects have been recognized that adversely impact Treg cell development, differentiation, and/or function, leading to heritable diseases of immune dysregulation and autoimmunity.