The aims of this paper were to describe clinical and laboratory details of 4 siblings, of whom 2 have systemic sclerosis and to describe this family in the context of reported cases of familial systemic sclerosis. The proband and his affected male sibling share the tissue typing antigens: HLA11, B57, DR13, DRw52,- and DQ2,6. Both were concordant for gender, silica exposure, marital status, migration history and antinuclear factor status but discordant for systemic sclerosis subtype, age at disease onset and ENA status. One non-affected sibling had no disease despite concordance for gender, HLA status, silica exposure, marital status, and migration history.

BACKGROUND: We report a case of primary immunodeficiency due to a defect of the TAP transporter, an heterodimeric complex which controls the expression of HLA class I molecule by delivering peptides from the cytosol into the lumen of the endoplasmic reticulum. Since childhood, the 36 year old female suffered from recurrent sinusitis/bronchitis. She later developed bronchiectasis and destructive nasal epitheloid granulomata in conjunction with a generalized vasculitic syndrome that did not improve upon immunosuppression and antibiotics.
METHODS: The class I monomorphic W6/32 was used for cell surface staining and immunoprecipitation of MHC class I molecules. Peptide transport assay was carried out in semi-permeabilized cells with iodinated peptides. Antigen presentation experiments were performed using chromium 51 labelled patient B cell line and EBV specific CTL. TAP1 and TAP2 specific antibodies were used for Western blotting and immunoprecipitation of the TAP complex.
CONCLUSIONS: A severe reduction of MHC class I molecules at the cell surface of the B-cell lines was observed, whereas MHC class II expression was not altered. Isoelectric focusing of metabolically labelled MHC class I molecules revealed that class I heavy chains remain unsialylated, consistent with a block of TAP dependent peptide translocation. These conclusions were confirmed by further experiments showing that peptide translocation was completely abolished. We also demonstrated that presentation of viral antigens through endogenous class I molecules was severely impaired. Immunoprecipitation and Western blotting of TAP1/2 complex showed that TAP2 was not detectable. Further, experiments are in progress to identify the site of the mutation.