Low percentages of regulatory T cells in common variable immunodeficiency (CVID) patients with autoimmune diseases and its association with increased numbers of CD4+CD45RO+ T and CD21low B cells.

BACKGROUND: Common variable immunodeficiency (CVID) is a heterogeneous group of primary antibody deficiencies defined by marked reductions in serum IgG, IgA and/or IgM levels and recurrent bacterial infections. Some patients are associated with defects in T cells and regulatory T cells (Tregs), resulting in recurrent viral infections and early-onset autoimmune disease. METHODS: We analyzed whether there is an association between Tregs cells (CD4+CD25+CD127low and CD4+CD25+FoxP3+); memory T cells (CD4+CD45RO+); memory B cells (CD19+CD27-IgD-); and CD21low B cells (CD19+CD38lowCD21low); as well as autoimmune manifestations in 36 patients with CVID (25 women and 11 men, mean age 24 years), all by flow cytometry. RESULTS: Fourteen patients presented with autoimmune diseases (AI) (39%), including 11 with autoimmune thrombocytopenia (ITP) (31%); two with vitiligo (6%); one with systemic lupus erythematosus (LES) (3%); and one with multiple sclerosis (MS) (3%). CVID patients with AI had a reduced proportion of Tregs (both CD4+CD25+CD127low and FoxP3+ cells) compared with healthy controls. CVID patients with AI had expanded CD21low B cell populations compared with patients who did not have AI. A correlation between increased CD4+CD45RO T cell populations and reduced Tregs was also observed. CONCLUSIONS: Our results showed that 39% of patients with CVID had AI and reduced Tregs populations. Research in this area might provide noteworthy data to better understand immune dysfunction and dysregulation related to CVID.

Clinical and mutational features of X-linked agammaglobulinemia in Mexico.

X-linked agammaglobulinemia (XLA) is caused by BTK mutations, patients typically show <2% of peripheral B cells and reduced levels of all immunoglobulins; they suffer from recurrent infections of bacterial origin; however, viral infections, autoimmune-like diseases, and an increased risk of developing gastric cancer are also reported. In this work, we report the BTK mutations and clinical features of 12 patients diagnosed with XLA. Furthermore, a clinical revision is also presented for an additional cohort of previously reported patients with XLA. Four novel mutations were identified, one of these located in the previously reported mutation refractory SH3 domain. Clinical data support previous reports accounting for frequent respiratory, gastrointestinal tract infections and other symptoms such as the occurrence of reactive arthritis in 19.2% of the patients. An equal proportion of patients developed septic arthritis; missense mutations and mutations in SH1, SH2 and PH domains predominated in patients who developed arthritis.

Lymphocytes and B-cell abnormalities in patients with common variable immunodeficiency (CVID).

BACKGROUND AND AIMS: Common variable immunodeficiency (CVID) is a primary antibody deficiency characterised by decreased antibody production and low or normal B-cell numbers. To elucidate the clinical and immunological heterogeneity of CVID, we studied 16 patients diagnosed with CVID. METHODS: We analysed B, T and NK cell populations. We also assessed CD27 expression to define B-cell subsets and examined the expression of molecules important in B-cell proliferation and differentiation, such as the transmembrane activator and CALM interactor (TACI), inducible costimulator (ICOS), CD154 and CD40. RESULTS: We observed reduced B and T-cell numbers in CVID patients; this reduction was more pronounced in adults. While one group of patients (group I) showed a significant reduction in CD27+ memory B-cells, another group (group II) of patients exhibited numbers of CD27+ memory B-cells similar to the healthy donor. The frequency of B-cells and T-cells expressing CD40 and ICOS, respectively, was significantly lower in all CVID patients compared with healthy donors. Finally, a correlation between the frequency of CD27+ memory B-cells and clinical features was observed in CVID patients. CONCLUSION: These results suggest that in some patients, the combined defects in both T and B-cells may account for CVID. Additionally, patients in group I exhibited an increased frequency of pneumonia and chronic diarrhoea.

Characterization of Bruton's tyrosine kinase mutations in Mexican patients with X-linked agammaglobulinemia.

X-linked agammaglobulinemia (XLA) is a humoral primary immunodeficiency in which affected patients have very low levels of peripheral B cells and a profound deficiency of all immunoglobulin isotypes. Mutations in the gene encoding for Bruton's tyrosine kinase (Btk) are responsible for most of the agammaglobulinemia. In this work, 14 Btk mutations responsible of causing XLA are described; eight of which are novel and six are mutations previously reported. Seven of the mutations were due to deletions and insertions of exons and introns, respectively, which suggest splicing defects. The others were missense mutations, five of which affect arginine residues and have been described, and two new which affect leucine and glutamine residues (L111P and E605G). Most of these mutations were located at the kinase domain of Btk and, less frequently, they were found in PH and SH2 domains. Protein expression was also affected since most of the patients did not express or express very low Btk.