Interplay of four idiotypes and interaction with autoantibodies in lupus patients, their relatives and their spouses.
Our aim was to investigate links between systemic lupus erythematosus (SLE)-associated autoantibodies, idiotypes (Id) and genetic predisposition to their development. We studied four public Ids (16/6, WRI 176 beta, RT72 and RT84), identified the Km and Gm phenotypes and sought six selected autoantibodies in 32 SLE patients, 174 of their relatives and 15 spouses. Though anti-double-stranded DNA antibody was uncommon in the relatives (9%), the range of antinuclear reactivities was as broad in the relatives as in the probands. Antibodies to the synthetic peptide U1-RNP-A 35-38 were found in 56% of the patients, 28% of their relatives and 20% of the spouses, whereas antibodies to the Golgi apparatus was present in 7% of the patients, 26% of their relatives and 33% of the spouses. However, most of these family members were unaffected. RT84 Id was positively associated with antibodies to Sm-D peptide 1-20 and to Ro/SSA 60 kD peptide 304-324, but negatively associated with anti-dsDNA activity. The median of age was significantly lower in the RT84 Id-positive than in the RT84 Id-negative individuals. These data suggest that genetic as well as environmental factors are involved in the aetiology of SLE. In addition, RT84-carrying immunoglobulins (Ab2) might be directed to one of many cross-reactive Ids of dsDNA-binding antibodies (Ab1), perhaps down-regulating their production.
Youinou
P
P
Brest University Medical School, France.
Isenberg
D A
DA
Kalsi
J K
JK
Dugoujon
J M
JM
Ravirajan
C T
CT
Muller
S
S
Blanco
F
F
Piette
J C
JC
Guillevin
L
L
Jouquan
J
J
Semana
G
G
Salmon
D
D
Shoenfeld
Y
Y
Bach
J F
JF
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000974:Antibodies, Antinuclear / Q000097:blood / Q000235:genetics; D000911:Antibodies, Monoclonal; D001323:Autoantibodies / Q000097:blood / Q000235:genetics*; D001324:Autoantigens; D003429:Cross Reactions; D005190:Family; D005260:Female; D006056:Golgi Apparatus / Q000276:immunology; D006801:Humans; D007126:Immunoglobulin Allotypes / Q000235:genetics; D007130:Immunoglobulin Idiotypes / Q000097:blood / Q000235:genetics*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology*; D008297:Male; D008393:Marriage; D008875:Middle Aged; D010375:Pedigree; D010446:Peptide Fragments / Q000276:immunology; D020733:RNA, Small Cytoplasmic; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000276:immunology; D012261:Ribonucleoproteins; D000099207:SS-A Antigen
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D001324:Autoantigens; D007126:Immunoglobulin Allotypes; D007130:Immunoglobulin Idiotypes; D010446:Peptide Fragments; D020733:RNA, Small Cytoplasmic; D017412:Ribonucleoprotein, U1 Small Nuclear; D012261:Ribonucleoproteins; D000099207:SS-A Antigen; C116006:RO60 protein, human