![]() ![]() RAG1 and RAG2 form the recombinase complex which binds and cleaves specific recombination signals that flank VDJ regions. To obtain the necessary level of diversity, the recombination of the variable (V), diversity (D) and joining (J) segments that form these receptors is directed by recombination activating gene 1 (RAG1) and 2 (RAG2). The adaptive immune system is critically dependent on the diverse expression of B cell immunoglobulin receptor (BCR) and T cell receptor (TCR). The specific roles of the authors are articulated in the author contributions section. Eibl, and did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Biomedizinische ForschungsgmbH provided no support in the form of salary for author Martha M. The specific roles of the authors are articulated in the author contributions section.Ĭompeting interests: The authors have declared that no competing interests exist. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedĭata Availability: All relevant data are within the paper and its Supporting Information files.įunding: Biomedizinische ForschungsgmbH provided no support in the form of salary for author Martha M. Received: DecemAccepted: JPublished: July 17, 2015Ĭopyright: © 2015 Geier et al. PLoS ONE 10(7):Įditor: Frederic Rieux-Laucat, Pavillon Kirmisson, FRANCE In conclusion, hypomorphic mutations in genes responsible for SCID should be considered in adults with predominantly antibody deficiency.Ĭitation: Geier CB, Piller A, Linder A, Sauerwein KMT, Eibl MM, Wolf HM (2015) Leaky RAG Deficiency in Adult Patients with Impaired Antibody Production against Bacterial Polysaccharide Antigens. after tetanus or TBEV vaccination was intact. Both patients presented with severely decreased numbers of naïve CD4 + T cells and defective T independent IgG responses to bacterial polysaccharide antigens, while T cell-dependent IgG antibody formation e.g. The second novel RAG2 mutation leads to a truncated RAG2 protein, lacking the C-terminus with intact core RAG2 and reduced VDJ recombination capacity as previously described in a mouse model. One of these novel mutations affected the start codon of RAG1 and resulted in an aberrant gene and protein expression. Both patients harbored a combination of a null mutation on one allele with a novel hypomorphic RAG1/2 mutation on the other allele. Clinical manifestation included recurrent pneumonia, sinusitis, otitis media and in one patient recurrent cutaneous vasculitis. Herein we describe a novel presentation of leaky RAG1 and RAG2 deficiency in two unrelated adult patients with impaired antibody production against bacterial polysaccharide antigens. In addition identification of hypomorphic mutations in RAG1 and RAG2 has led to an expansion of the spectrum of disease to include Omenn syndrome, early onset autoimmunity, granuloma, chronic cytomegalovirus- or EBV-infection with expansion of gamma/delta T-cells, idiophatic CD4 lymphopenia and a phenotype resembling common variable immunodeficiency. Loss of function mutations in the recombination activating genes RAG1 and RAG2 have been reported to cause a T -B -NK + type of severe combined immunodeficiency.
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