Allergy, Asthma & Clinical Immunology

Presenting processed antigens to CD4+ lymphocytes during the immune response involves major histocompatibility complex class II molecules. MHC class II genes transcription is regulated by four transcription factors: CIITA, RFXANK, RFX5 and RFXAP. Defects in these factors result in major histocompatibility complex class II expression deficiency, a primary combined immunodeficiency frequent in North Africa. Autosomal recessive mutations in the RFXANK gene have been reported as being the principal defect found in North African patients with this disorder. In this paper, we describe clinical, immunological and genetic features of 11 unrelated Algerian patients whose monocytes display a total absence of MHC class II molecules. They shared mainly the same clinical picture which included protracted diarrhoea and respiratory tract recurrent infections. Genetic analysis revealed that 9 of the 11 patients had the same RFXANK founder mutation, a 26 bp deletion (named I5E6-25_I5E6+1, also known as 752delG26). Immunological and genetic findings in our series may facilitate genetic counselling implementation for Algerian consanguineous families. Further studies need to be conducted to determine 752delG26 heterozygous mutation frequency in Algerian population. Background Major histocompatibility complex (MHC) class II deficiency or Bare lymphocyte syndrome (BLS) type II is a primary immunodeficiency, characterized by partial or total absence of constitutive and induced MHC class II molecules (DR, DQ and DP) surface expression on cells normally expressing them [1-3]. Expression of DR, DQ and DP genes is controlled by four transcription factors encoded by four different genes, CIITA (MIM 600005), RFXANK (MIM 603200), RFX5 (MIM 601863) and RFXAP (MIM 601861) [4-7]. Defects in these factors results in BLS type II and determine four groups of complementation, respectively, A, B, C and D [8-11]. Transcription factors RFXANK, * Correspondence: [email protected] Equal contributors Immunology Department, Beni Messous Teaching Hospital, Algiers, Algeria Full list of author information is available at the end of the article © 2012 Djidjik et al.; licensee BioMed Central L Commons Attribution License (http://creativec reproduction in any medium, provided the or RFX5 and RFXAP associate to form the RFX complex [12] which allow, together with CIITA [7,13,14], CMH class II gene expression. The absence of CMH class II molecules surface expression on antigen-presenting cells is behind impaired immune responses in patients with BLS, who present then, a combined immunodeficiency of early-onset. These individuals are prone to severe and recurrent respiratory and digestive tract infections; whether they are bacterial, viral or fungal. Intestinal infections lead to malabsorption and thereby a failure to thrive. The average life expectancy of these patients is 4 years [15]. A high consanguinity rate has been noted in affected families, whatever the complementation group to which they belong. MHC class II deficiency is inherited as an autosomal recessive trait. Since the first description of this disease, about 150 patients have been reported [16]. Although, this disorder is observed in different ethnic td. This is an Open Access article distributed under the terms of the Creative ommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and iginal work is properly cited. Djidjik et al. Allergy, Asthma & Clinical Immunology 2012, 8:14 Page 2 of 5 http://www.aacijournal.com/content/8/1/14 groups, North African population remains the most frequently affected [11,17]. The majority of North African patients belong to complementation group B. These patients have, mostly, the same mutation in the RFXANK gene: a 26 bp deletion at the boundary between intron 5 and exon 6 named I5E6-25_I5E6+1 (also known as 752delG-25) [11] which has been found in more than 90% of North African families [18]. This gene encodes a transcription factor of 260 amino acids. It is composed of ten exons spanning approximately 10 Kb and is located on chromosome 19p12 [5,19]. No genetic study of patients with BLS type II has ever been conducted in Algeria. Here we report clinical and genetic features of eleven Algerian MHC class II deficiency patients, in the light of immunological abnormalities.