HLA class I deficiency as an additional cause of bronchiectasis.

We read with interest the recent paper by Guan et al. about the aetiology of bronchiectasis in Guangzhou, southern China.1 The authors find that idiopathic, post-infectious and immunodeficiency-related causes are the most common origins of this syndrome. The idiopathic form is likewise a predominant aetiology in similar studies performed in other countries, as the authors well present. Bronchiectasis is considered as idiopathic after the exclusion of all known aetiologies.1 However, although we do not want to criticize this important and considerable work, we nevertheless would like to mention that one possible cause has not been eliminated in this study, namely Human Leukocyte Antigen (HLA) class I deficiency syndrome, which is in most cases the result of a defect either in one of the transporter associated with antigen processing (TAP1 or TAP2) genes or in the b2-microglobulin (b2m) gene.2,3 In both situations, the expression level of HLA class I molecules at the cell surface is extremely low,2,3 and at least in TAP deficiency, most patients have in addition to necrotizing skin ulcers due to bacterial infection also chronic bacterial infections of the airways which frequently evolve to bronchiectasis even at a young age.2 Although predominantly ab CD8+ T cells are affected in this disease, the patients do not suffer from severe viral infections, which might nevertheless contribute to the overall airway pathology due to a potentially insufficient viral clearance.2
Up to now, only 33 cases of TAP deficiency have been confirmed at the molecular level. One could therefore conclude that this disease is extremely rare. However, given the very high number of cases labelled as idiopathic bronchiectasis, it could well be that a substantial fraction of those in fact corresponds to HLA class I deficiencies and would therefore have a clear and precise aetiology.
Therefore, we propose, as already several times before,4,5 to systematically include the screening for this defect into the biological investigations of bronchiectasis cases. The argument of the authors that cellular immunodeficiencies are complicated and costly1 would not be so valid in this situation, because it is cost-effective and easy to stain whole blood cells from the patients with a fluorochrome-conjugated pan anti-HLA class I antibody and then to analyze the expression level of HLA class I molecules by flow cytometry, in comparison with cells from a healthy control donor.