Differential contribution of HLA-DR, DQ, and TAP2 alleles to systemic lupus erythematosus susceptibility in Spanish patients: role of TAP2*01 alleles in Ro autoantibody production

doi:10.1136/ard.57.4.214

Annals of the Rheumatic Diseases 1998;57:214-219; doi:10.1136/ard.57.4.214

Ann Rheum Dis 1998;57:214-219 ( April )

Extended reports

Differential contribution of HLA-DR, DQ, and TAP2 alleles to systemic lupus erythematosus susceptibility in Spanish patients: role of TAP2*01 alleles in Ro autoantibody production José M Martín-Villa,^a Jorge Martínez-Laso,^a Miguel A Moreno-Pelayo,^a Maria J Castro-Panete,^a Narcisa Martínez-Quiles,^a Miguel Alvarez,^a Maria D de Juan,^c Juan J Gómez-Reino,^b Antonio Arnaiz-Villena^a

^a Departments of Immunology, ^b and Rheumatology, ^c Hospital Universitario "12 de Octubre", Universidad Complutense, 28041 Madrid, Spain Department of Immunology, Hospital Nta, Sra de Aránzazu, San Sebastián, Spain

Correspondence to: Dr A Arnaiz-Villena.

Accepted for publication 4 February 1998.

OBJECTIVE $---$ To study the influence MHC class II and TAP2 alleles exert on systemic lupus erythematosus (SLE) susceptibility and on theclinical and serological manifestations of the disease, in a cohortof Spanishpatients.
METHODS $---$ HLA-DR serological typing and HLA-DQA, DQB, and TAP2 DNA sequence specific oligotyping, were carried out in 85 unrelated SpanishSLE patients and 186 healthy controls. Autoantibodies detectionwas carried out by indirect immunofluorescence and counterimmunoelectrophoresis.
RESULTS $---$ Total SLE group: the frequency of HLA-DR3 and HLA-DQA1*0501 is significantly increased in this group (p_c<0.005, $delta$ =0.34 andp_c<0.005, $delta$ = 0.45, respectively) although the highest $delta$ value( $delta$ =0.87) is obtained when the TAP2*01 alleles are considered.No DQB allele shows significant deviation from the control group.Renal damage: it mainly occurs in HLA-DR3 patients (p_c<0.0005and $delta$ =0.72). HLA-DQA1*0501 (p_c<0.05, $delta$ =0.57) and DQB1*0201 (p_cNS, $delta$ =0.56) are weaker susceptibility factors. Ro+ (but not La)group: this autoantibody response is associated with TAP2*01 allelesin homozygosity (p<0.05, $delta$ =0.81). Ro/La+ group: it has a differentgenetic background as HLA-DQA1*0501 ( $delta$ =1) and HLA-DQB1*0201 ( $delta$ =1)are the main susceptibilityfactors.
CONCLUSIONS $---$ A differential association between HLA-DR, DQA1, and DQB1 alleles and SLE or its clinical and serological manifestations arefound. Furthermore, the associations are different to the onesreported in other ethnic groups. Finally, TAP2*01 group of allelesare associated with the highest susceptibility to SLE (higherthan HLA-DR3) and may influence Ro (but not La) autoantibodiesproduction, whereas HLA-DQA1*0501 and DQB1*0201 mediates concomitantRo and Laproduction.

Keywords: TAP2 alleles; HLA class II alleles; systemic lupus erythematosus

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