Bare lymphocyte syndrome, type1; D81.6

Bare lymphocyte syndrome, type I (BLS) is a very rare autosomal recessive disorder of lymphocyte function caused by mutations in the TAP2 (170261), TAP1 (170260) or TAPBP (601962) gene and is due to MHC class I deficiency.

TAP is the acronym for "Transporter associated with antigen processing". It is a protein complex consisting of two proteins located in the membrane of the endoplasmic reticulum (ER) and is found in animals and fungi. The antigen peptide transporter TAP is a transport protein of the ABC transporter family. TAP translocates antigenic peptides into the lumen of the endoplasmic reticulum (ER) for loading onto MHC class I molecules. This antigen presentaion is an important step in the control of viral infections by CD8+ T cells.

In the review by de la Salle et al. (1999), only 9 well-documented cases of HLA class I deficiency with normal expression of class II molecules were found. In contrast to type II (209920) and type III bare lymphocyte syndromes, which are characterized by the early onset of a severe combined immunodeficiency, class I antigen deficiencies are not accompanied by specific disease symptoms in the first years of life. Chronic lung disease develops in late childhood. Also, unlike type II or type III BLS, diarrhea is not observed.

Systemic infections have not been described in patients with HLA class I deficiency. Chronic bacterial infections, often beginning in the first decade of life, are confined to the respiratory tract and extend from the upper to the lower airways. Bronchiectasis, emphysema, panbronchiolitis, and bronchial obstruction have been described. De la Salle et al (1999) noted a high incidence of nasal polyps and and paranasal sinus involvement.

Moins-Teisserenc et al (1999) described 5 patients with a syndrome of chronic necrotizing granulomatous lesions, small vessel vasculitis, recurrent respiratory infections and the development of bronchiectasis. The diagnosis of granulomatosis with polyangiitis was considered but discarded because of incompatible disease course and resistance to immunosuppressive treatments. All 5 patients had severely decreased cell surface expression of HLA class I molecules and defective expression of the TAP complex.

1. de la Salle H et al. (1999) HLA class I deficiencies.In: Ochs, H. D.; Smith, C. I. E.; Puck, J. M. (eds.): Primary Immunodeficiency Diseases: A Molecular and Genetic Approach. New York: Oxford University Press 1999: 181-188.
2. de la Salle H et al (1994) Homozygous human TAP peptide transporter mutation in HLA class I deficiency. Science 265: 237-241
3. Moins-Teisserenc H T et al (1999) Association of a syndrome resembling Wegener's granulomatosis with low surface expression of HLA class-I molecules. Lancet 354: 1598-1603