Heritable factors shape natural human IgM reactivity to Ro60/SS-A and may predispose for SLE-associated IgG anti-Ro and anti-La autoantibody production.
Systemic lupus erythematosus (SLE) is characterized by various IgG autoreactivities, among which anti-Ro/SS-A is particularly pathology-associated and early detectable. SLE also shows significant familial aggregation, but genetic factors are not well understood and remain controversial for disease-associated IgG. Here we report that IgM anti-Ro showed a uniquely high degree of heritability in a study of SLE-affected families. Unlike IgM anti-La or anti-dsDNA, IgM anti-Ro was also significantly correlated to IgG anti-Ro among SLE patients, as well as to IgG anti-La and anti-dsDNA. We conclude that largely genetically determined, thus natural IgM anti-Ro-bearing precursor B-cells, may be an important factor for class switching and determinant spreading in early phases of SLE pathogenesis. Furthermore, we found unexpected sex differences in isotype/specificity correlations among SLE-unaffected relatives and control subjects, which could help understand the strong gender bias associated with SLE. We propose that the study of such correlation structures may reveal characteristic spreading pathways relevant for human SLE.
Ferreira
Ricardo
R
Instituto Gulbenkian de Ciência, Apartado 14, 2781-901 Oeiras, Portugal.
Barreto
Marta
M
Santos
Eugénia
E
Pereira
Clara
C
Martins
Berta
B
Andreia
Rita
R
Crespo
Francisco
F
Viana
João Faro
JF
Vasconcelos
Carlos
C
Ferreira
Carlos
C
Vicente
Astrid Moura
AM
Fesel
Constantin
C
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000974:Antibodies, Antinuclear / Q000096:biosynthesis* / Q000378:metabolism*; D001324:Autoantigens / Q000276:immunology*; D002648:Child; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007075:Immunoglobulin M / Q000378:metabolism*; D016014:Linear Models; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D012261:Ribonucleoproteins / Q000276:immunology* / Q000378:metabolism; D012737:Sex Factors; D000097585:SS-B Antigen; D000099207:SS-A Antigen
D000974:Antibodies, Antinuclear; D001324:Autoantigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D012261:Ribonucleoproteins; D000097585:SS-B Antigen; D000099207:SS-A Antigen; C035356:SS-A antibodies; C035357:SS-B antibodies