B cells spot classes of immunodeficient patients
Antibodies are large proteins, mainly produced by B-cells and employed by the immune system to identify and combat bacteria and viruses. Low levels or absence of particular antibodies leads to increased susceptibility of individuals to infections, called immunodeficiency. Primary antibody deficiencies (PAD) are listed among rare, chronic, non-infectious disorders. They have been associated with recurrent sinusitis, bronchitis or even pneumonia, hence, there is increasing interest on developing new methods for early diagnosis and treatment. PAD has been classified into three subclasses, according to immunoglobulin (Ig) antibody levels. These are selective IgA deficiency (IgAD), the non-X-linked hyper-IgM syndrome and the common variable immunodeficiency (CVID). IMPAD partners aim to contribute to prognosis and treatment of PADs improving clinicians' tools for diagnosis and patients' well being. Their efforts focus on B cell activation and differentiation defects that induce PADs. In this frame, an improved rapid and reliable classification of CVID, the most common form of PAD, was performed. Researchers managed to determine the correlation between class-switched memory B-cells available and immunoglobulin isoforms (IgG, IgA) concentration. The results obtained revealed that CVID patients could be further arranged in two categories. Type I patients (75% of all CVID patients) were deficient of class-switched memory B cells and failed to produce IgG and IgA in vivo and in vitro. In the case of type II patients (25%) B cells were present and produced IgG and IgA in vitro, however at low concentrations. Other studies in a partner's laboratory, revealed that a subset of type I patients was missing both IgM and class-switched memory B cells, enhancing the suggested categorization. Subclassification of type I patients using a sample of >300 CVID patients is almost complete. IMPAD partners anticipate disseminating their results to PAD centres for the development of new diagnostics beneficial for patients and professionals.
