The 1966 annual meeting of the American Rheumatism Association.
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Biomedical subjects
Publications and source records attributed to N Talal.
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Antibodies of polyriboadenylic acid (poly rA) are demonstrated by filter radioimmunoassay in 75% of patients with systemic lupus erythematosus (SLE), in 54% of patients with discoid lupus erythematosus, and in only 0-7% of normal controls and patients with rheumatoid arthritis or Sjögren's syndrome. These antibodies are distinct from antibodies to single- and double-stranded DNA and double-stranded RNA. Poly rA binding is associated with IgM and IgG serum fractions. Because poly rA may have a role in the transcription of mRNA in mammalian cells and viruses, antibodies to poly rA may be important clues to virologic and immunogenetic mechanisms in the pathogenesis of SLE.
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Antibodies to double-stranded DNA (DSDNA) were found in 18 patients with RA, in 5 patients with JRA, and in 5 patients with undiagnosed connective tissue disease. Five patients had clinical features consistent with both RA and SLE, 11 with only RA, and 5 with only JRA. Based on these observations, the presence of serum anti-DSDNA antibodies should not be used as a sole criterion in the diagnosis of SLE.
Autoantibodies in Sjögren's syndrome (SS) were identified by their precipitin reactions with tissue antigens in immunodiffusion. The source of antigens was a sonicated extract of human lymphoid cells (WiI2) grown in tissue culture. Three distinct precipitin systems were identified and referred to as precipitins SS-A and SS-B, and rheumatoid arthritis precipitin. These studies show that precipitins SS-A and SS-B are present in high frequency in sera of patients with SS without associated rheuamtoid arthritis (RA) and are absent or present in low frequency in many other connective tissue diseases. On the other hand patients with SS who also had clinical features compatible with RA (SS-RA) did not have precipitins SS-A and SS-B but had rheumatoid arthritis precipitin (RAP). The latter precipitin was also present in RA patients in a similar order of frequency as in SS-RA. All three precipitin systems were shown to be reactions betweeen immunoglobulins and cellular antigens. The origin of SS-A and SS-B antigens was demonstrated by immunofluorescence to be primarily from the nucleus but the origin of RAP in the cell has not been established.
HLA antigens were examined by microdroplet lymphocyte cytotoxicity in 31 patients with Sjögrens syndrome. Fifty percent of 22 Causcasian patients (7 of 17 females and 4 of 5 males) had HLA-B8, as compared to 21% of 1205 controls (P=0.002). The presence of HLA-B8 was not correlated with parotid salivary flow, keratoconjunctivitis sicca, or focus score. Because of its association with a number of autoimmune diseases, including Sjögren's syndrome, it is suggested that HLA-B8 is genetically liked to an immune response gene(s) that predisposes the individual to autoimmune phenomena. The expression of autoimmunity may be determined by infectious or environmental factors.
Sera from six sets of twins (five monozygotic and one dyzygotic) in whom one or both has systemic lupus erythematosus (SLE) were evaluated for antibodies to DNA and RNA. Sera from three monozygotic twin sets were further studied to determine the distribution of 19S and 7S antibodies to DNA and RNA. The presence of significant binding of polyriboadenylic acid and of native DNA correlated with the presence of clinical SLE in this study. Sucrose density gradient fractionation studies of the sera revealed that the clinically normal twins had some binding of Poly A and DNA limited to the 19S region, whereas the twins with SLE generally had significant levels of 19S and 7S antibodies to DNA and/or Poly A. On the other hand, concordance for presence or absence of antibodies to doublestranded RNA was demonstrated within each twin set irrespective of concordance or discordance for clinical SLE. These results suggest that genetic factors may be important in determining which nucleic acids antigens become immunogenic, but genetic factors alone do not determine the immunoglobulin class distribution of antibodies to nucleic acids.
Antilymphocyte, antipolynucleotide, and antiviral antibodies in 15 Soviet systemic lupus erythematosus (SLE) probands and their 41 relatives were compared with those in 57 members of 15 control Russian families. Seventy-eight and three-tenths percent of SLE relatives were positive for antilymphocyte antibody versus 26.3% positive reactions in controls. Antipolynucleotide antibody closely paralleled antilymphocyte antibody in both groups. Antiviral antibody was significantly increased in SLE relatives as compared to control family members. No correlation was noted between quantitative IgG, IgA, or IgM levels and various antibodies studied.