TNFRSF13B encodes transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI), a B cellspecific tumor necrosis factor (TNF) receptor superfamily member. Both biallelic and monoallelic TNFRSF13B mutations were identified in patients with common variable immunodeficiency disorders. The genetic complexity and variable clinical presentation of TACI deficiency prompted us to evaluate the genetic, immunologic, and clinical condition in 50 individuals with TNFRSF13B alterations, following screening of 564 unrelated patients with hypogammaglobulinemia. We identified 13 new sequence variants. The most frequent TNFRSF13B variants (C104R and A181E; n ‫؍‬ 39; 6.9%) were also present in a heterozygous state in 2% of 675 controls. All patients with biallelic mutations had hypogammaglobulinemia and nearly all showed impaired binding to a proliferationinducing ligand (APRIL). However, the majority (n ‫؍‬ 41; 82%) of the patients carried monoallelic changes in TNFRSF13B. Presence of a heterozygous mutation was associated with antibody deficiency (P <.001 , relative risk 3.6). Heterozygosity for the most common mutation, C104R, was associated with disease (P < .001, relative risk 4.2). Furthermore, heterozygosity for C104R was associated with low numbers of IgD ؊ CD27 ؉ B cells (P ‫؍‬ .019), benign lymphoproliferation (P < .001), and autoimmune complications (P ‫؍‬ .001). These associations indicate that C104R heterozygosity increases the risk for common variable immunodeficiency disorders and influences clinical presentation. (Blood.

Otherwise restricted to patients with thymoma and/or myasthenia gravis, these precocious persistent antibodies show 98% or higher sensitivity and APS-I specificity and are thus a simpler diagnostic option than detecting AIRE mutations.

Thymus-derived cells of the mouse, rat, and human can be divided, on the basis of differential expression of cell surface antigens, into phenotypically distinct subsets, and this phenotypic heterogeneity is correlated with functional differences (1-3). In the rat, the monoclonal antibody W3/25 (5) has been shown to label the T subset that contains helper cells for B cells (5) and cytotoxic T cells (6, 7) and also cells that mediate graft-versus-host (GvH) 1 reactivity (5). The monoclonal antibody MRC OX-8 labels the subset that contains suppressor and cytotoxic activities (2,6,8).In this paper a new monoclonal antibody MRC OX-22 is described that labels a subset of the W3/25 ÷ cells in the rat. Data are presented demonstrating that this phenotypic division is correlated with a functional one, with cells mediating help for B cells and those mediating GvH reactivity in different T cell subsets. Biochemical studies of the MRC OX-22 antigen demonstrate that it reacts with the high molecular weight form of the rat leukocyte-common antigen (L-CA). Materials and Methods RatsInbred rats from the specific pathogen-free unit at the MRC Cellular Immunology Unit were used. The strains were PVG/c (RTlC; Iglb), PVG-1 a (RTlC; Igla), and (PVG × DA)F~ (RTV × RTI"). PVG/c and PVG-I" are congenic strains that differ in their immunoglobulin light chain allotypes. Irradiations were performed using a 137Cs source at 94 rad/min (Gammacel; Atomic Energy of Canada).

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22q11.2 deletion syndrome is the commonest chromosome deletion syndrome. 22q11.2 deletion may result in variable clinical phenotypes which may differ even between patients with identical deletions. Abnormal pharyngeal arch development results in defects in the development of the parathyroid glands, thymus and conotruncal region of the heart. Defective thymic development is associated with impaired immune function. ‘Complete’ DiGeorge syndrome with total absence of the thymus and a severe T‐cell immunodeficiency accounts for <0.5% of patients. The majority of patients with 22q11.2 deletion syndromes have ‘partial’ defects with impaired thymic development rather than complete absence with variable defects in T‐cell numbers. Immunodeficiency in these patients is not solely due to T‐cell deficiency and abnormalities of T‐cell clonality or impairment of proliferative responses may play a role. Humoral deficiencies including defects in the B‐cell compartment have also been identified in these patients. 22q11.2 deletion syndrome patients are at increased risk of a variety of autoimmune diseases. A number of immune defects may predispose to the development of autoimmunity in these patients including increased infection, impaired development of natural T‐regulatory cells and impaired thymic central tolerance.