Presence of rheumatoid factor and antibodies to citrullinated peptides in systemic lupus erythematosus.
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Biomedical subjects
Publications and source records attributed to L Cebecauer.
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OBJECTIVES: To study associations between antinuclear antibodies (ANA) and signs/symptoms in patients with systemic lupus erythematosus (SLE). METHODS: A consecutive cohort of 289 patients with SLE was included; 235 fulfilled ACR criteria for SLE and were further analysed. ANA profiles were determined by line immunoassay and by indirect immunofluorescence on Crithidia luciliae. An extensive list of signs/symptoms was evaluated. RESULTS: Five clusters of antibodies were defined by cluster analysis: 1-antibodies to SmB, SmD, RNP-A, RNP-C, and RNP-70k; 2-antibodies to Ro52, Ro60, and SSB; 3, 4, and 5-antibodies to ribosomal P, histones and dsDNA, respectively. Significant associations (p< or =0.01) were found between anti-RNP-70k, anti-RNP-A, anti-RNP-C and Raynaud's phenomenon, between anti-RNP-A, anti-RNP-70k and leucopenia, and between anti-RNP-A, anti-RNP-C and a lower prevalence of urine cellular casts. Anti-SSA, anti-SSB were associated with xerostomia, and anti-SSB with pericarditis. Antibodies to ribosomal P were associated with haemolytic anaemia, leucopenia, and alopecia. Patients with anti-dsDNA antibodies had a higher risk for cellular casts and a lower risk for photosensitivity. Antihistone antibodies were associated with arthritis. CONCLUSIONS: In a large and consecutive cohort of patients with SLE, clusters of antibodies were identified. Previously reported associations of antibodies with symptoms were confirmed and new associations found.
Antibodies (Abs) against the structure specific recognition protein 1 (SSRP1) were reported in a small systemic lupus erythematosus (SLE) series but not in other systemic autoimmune diseases. The aim of the study was to confirm the selective presence of anti-SSRP1 Abs in a larger SLE series and to evaluate their relationship with disease activity and other immune markers. Anti-SSRP1 Abs were investigated by a 'home made' ELISA in: 120 SLE, 65 rheumatoid arthritis (RA), 51 systemic sclerosis (SSc), 23 Churg-Strauss syndrome (CSS) and 40 idiopathic autoimmune urticaria (IAU) patients and 190 healthy controls. Sera from MRL lpr/lpr and Balb-c mice were also tested. Anti-SSRP1 Abs were detected in 43 SLE (35.8%), nine SSc (17.6%), eight RA (12.3%), six IAU (15%), three CSS (13%) patients and five healthy controls (2.6%). Antibody prevalence and titers were significantly higher in SLE patients than in sera from both normal and disease controls. Anti-SSRP1 Ab activity was also detected in sera from MRL lpr/lpr but not Balb-c mice. The antibodies did not correlate with the disease activity evaluated as the ECLAM index score and were more prevalent in patients without renal involvement. No correlation was found with other serum autoantibodies. Our results confirm that anti-SSRP1 Abs are associated with but not specific for the lupus disease.
We investigated the relationships between prolactin (PRL) levels and antibody occurrence in systemic lupus erythematosus (SLE). No significant association between PRL levels and the majority of the autoantibodies studied (anti-U1 RNP, anti-rRNP, anti-Sm, anti-dsDNA, anti-DNP, auto-LCA, anti-EACA) could be confirmed (P > 0.05), anti-Ro/SSA antibodies being an exception. Our results showed significantly increased frequencies of these antibodies in the group of female SLE patients with normal PRL levels (< 20 micrograms/L): anti Ro/SSA in 53% (P < 0.025, chi 2 = 5.80, RR = 4.0) and anti-Ro/SSA + anti-Ro/La in 60% (P < 0.05, chi 2 = 4.05) compared with female SLE patients with hyperprolactinemia.
The authors review recent findings pertaining to the pathogenesis of systemic lupus erythematosus. It was revealed that knowledge of impaired humoral and cellular immunity is of great practical importance and substantially improves the prognosis of the disease.
The influence of charged polymers on the reaction of immunoglobulins from human lupus sera with cellular proteins was investigated in this study. Through immunoblotting it was shown that polyanions (dextran sulfate, heparin, polyinosinic acid) and polylysine inhibited autoantibody binding to several polypeptides of different molecular mass. Using immunofluorescent staining with affinity isolated monospecific autoantibodies it was demonstrated that the immunoreactivity of two nuclear antigens (p30 and p85) and one cytoplasmic antigen (p40) was sensitive to the presence of charged polymers. The inhibiting effect correlated with the concentration of the polymers. The data obtained suggested the competitive mechanism of inhibition of autoantibody-protein reaction by the charged polymers.
To study the possible involvement of a murine leukemia virus (MuLV) related agent in human cancer, an extensive immunoblotting analysis of human sera (cancer, autoimmune as well as control normal ones) for the presence of antibodies to MuLV structural proteins was performed. Out of 350 sera, 89 reacted with gag precursor Pr65, 72 reacted with major viral core protein p30 and five with the matrix protein p15. Antibody reactivity to the env-encoded glycoprotein gp70 was detected in 7 cases out of 16 sera tested. There were no significant differences between pathological and normal sera concerning the patterns and the frequency of the reactivity. Sera from patients with various malignancies (mainly with breast cancer) generally displayed more intensive signals to MuLV p30 than normal sera. Epitope mapping revealed that MuLV p30-reactive antibodies recognize an antigenic determinant(s) located at the carboxyterminus of the protein.
Using the Western blot method, the authors analyzed 85 sera obtained from patients with rheumatic diseases, focused on the presence of antihistones and antiactin autoantibodies. The authors detected a 32% incidence of the two investigated autoantibody specificities. In a group of 42 patients with systemic lupus erythematosus in 22 sera (52%) positive antihistone antibodies were present, whereby autoantibodies anti-H1 and anti-H2B were most frequent. In 15 sera in this group of patients (36%) antiactin autoantibodies were present.
Serum beta-2-microglobulin was examined by radioimmunoassay in 103 patients with ankylosing spondylitis and 111 healthy blood-donors. Statistically significant difference between the group of patients and healthy individuals was found related to increased levels of this protein in patients with ankylosing spondylitis. Furthers correlation analysis of beta-2-microglobulin in patients with ankylosing spondylitis and chosen clinical and humoral parameters of the disease activity was performed. Positive, statistically significant correlation with erythrocyte sedimentation rate, plasmatic gamma globulins, duration of morning stiffness and global activity of the disease was proved. Higher levels of beta-2-microglobulin in patients with ankylosing spondylitis could be attributed to activation of monocyte macrophages system in subpopulation of cytotoxic T-lymphocytes, which might be the evidence of the involvement of cytotoxic-T cell mechanisms in the pathogenesis of this disease.
ELISA was elaborated for the determination of antibodies against liver antigen complexes--submitochondrial particles, F1-ATPase and liver specific lipoprotein. The parameters achieved so far allow to use the assay as an undemanding complementary laboratory technique in diagnosing and monitoring hepatopathies of autoimmune origin. Cross reactivity between individual antigen complexes was recorded in the majority of sera from positively reacting patients. The preliminary results show that individual antigen complexes have similar antigen structures bound to high-molecular membrane complexes, some of which, however, can be solubilized on maintaining antigen activity in ELISA.
The authors investigated the incidence of antibodies against Klebsiella pneumoniae and E. coli in a group of patients with ankylosing spondylitis and in a group of healthy controls in all main immunoglobulin classes. The results revealed that in patients with ankylosing spondylitis there is a significantly higher incidence of specific antibodies of class IgA against Klebsiella pneumoniae and E. coli. This supports the thesis on the aetiopathogenetic interrelationship between enteric bacteria and the development of ankylosing spondylitis.
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Antibodies against denatured, single-stranded deoxyribonucleic acid were measured in the sera of children, young adults and old persons by means of a solid phase enzyme-linked immunosorbent assay using a peroxidase-labelled second antibody. Considerable amounts of anti-deoxyribonucleic acid antibodies were found in subjects in all the age groups studied. Mean serum activity in children and old persons was two times as high as that in young adults. Close correlation was observed in old age between the level of antibodies against single-stranded deoxyribonucleic acid and disorders of lipid metabolism, namely hypertriglyceridemia and hypercholesterolemia. Based on their finding that substantial quantities of antibodies of the above type appear to be present in healthy humans at different stages of ontogenesis, the authors suggest these autoantibodies may play, in addition to pathological, some physiological role.
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