Crossing of antinuclear antibodies and anti-leishmania antibodies

Visceral leishmaniasis or Kala-azar is an endemic parasitic infection in Mediterranean countries. We report an interesting case occurring in a 38-year-old woman suffering from systemic lupus erythematosus and secondary antiphospholipid syndrome. In our patient visceral leishmaniasis occurred during high dose-steroids treatment mimicking a flare of lupus. As the lupus resolved under immunosuppressive treatment, a reactivation of visceral leishmaniasis was observed and was confirmed by the successive serological tests which showed crossing of leishmania and antinuclear antibody titers. Our case shows that, faced with fever occurring in lupus patients in an endemic area, visceral leishmaniasis should be searched for before intensifying immunosuppressive treatments.     

Significance of antinuclear anti-histone antibodies

The results of routine antihistone antibody (AHA) assay in a preliminary series of 189 sera are presented. There were 23 positive tests (systemic lupus erythematosus, 8 cases; drug induced SLE, 4 cases; rheumatoid arthritis 7 cases; and multiple sclerosis, 1 case; chronic active hepatitis, 1 case; systemic sclerosis, 1 case and primary biliary cirrhosis 1 case). The results of routine assay in 5 other patients groups are reported: 30 spontaneous SLE (9 positive AHA), 63 rheumatoid arthritis (2 positive AHA), 19 Sj?gren syndrome (no AHA), 11 primary biliary cirrhosis (1 positive AHA) and 7 mixed connective tissue disease (no AHA).     

Speckled pattern antinuclear antibodies resembling anticentromere antibodies

Two distinct nuclear antigens, designated NSpI and NSpII, have been characterized and differentiated from the centromeric antigen that reacts with sera from patients with the CREST syndrome. Both NSpI and NSpII produce a speckled pattern of indirect immunofluorescence on HEp-2 cells that resembles the pattern seen with anticentromere antibodies (ACA). They are differentiated from the ACA staining pattern by the absence of metaphase chromatin staining by NSpI antisera and by the absence of a discrete speckled pattern of staining by NSpII. Further, both NSpI and NSpII stain predominantly the peritubular nuclei of mouse kidney cryostat sections. NSpII is sensitive to trypsin, proteinase K, and HCI extraction, suggesting that it is a relatively soluble nuclear protein. NSpI was also sensitive to protease treatment but was not extracted with 0.1N HCl, suggesting that it is a tightly bound nuclear protein.     

Complement-activating abilities of defined antinuclear antibodies

A complement-fixing immunofluorescence assay on HEp-2 cells was used to assess the ability of various antinuclear antibodies (ANA) to activate complement. Sera which contained only specific antibodies to nuclear RNP, SS-B/La, centromere, Sm antigen, double-stranded DNA, and/or nuclear histone were selected. Relative abilities of various ANA to activate complement were determined from the ratio of titers of C3, C4, or properdin-fixing ANA to the IgG ANA titers. Nuclear RNP-anti-RNP complexes activated and deposited significantly more complement C3 than other ANA (P less than 0.02). Antibodies to SS-B/La, centromere, and Sm activated more complement than anti-DNA or antihistone (P less than 0.02). Antihistone antibodies activated the least complement. These studies demonstrate that different ANA have significantly different orders of complement-activating capabilities when bound to their respective nuclear antigens.     

Immunogenetic associations of scleroderma-related antinuclear antibodies

Patients selected for the presence of scleroderma-related antibodies (anti-DNA-topoisomerase I [anti-topo I; n = 43], anticentromere antibody [ACA; n = 63], or anti-Pm-Scl [n = 12]) were studied for class I and class II major histocompatibility complex antigens, as well as for Gm and Km allotypes. Anti-topo I was associated with HLA-DR5 (70% of patients versus 30.6% of controls; Pcorr = 0.0018, relative risk [RR] = 5.3). All patients with anti-Pm-Scl were positive for HLA-DR3 (versus 23.5% of controls; Pcorr less than 0.001); 6 of these patients were DR3/4 heterozygous (50% versus 3.5% of controls; Pcorr less than 0.001, RR = 27.3). Patients with ACA were frequently positive for HLA-DR1, DR4, or DRw8, with 73.7% demonstrating at least 1 of these alleles (versus 41.2% of controls; Pcorr = 0.0152, RR = 4.0). This group of ACA-positive patients who had DR1, DR4, and/or DRw8 consisted mainly of a subgroup of patients with rheumatoid arthritis. We conclude that different class II major histocompatibility complex antigens influence the formation of anti-topo I and anti-Pm-Scl. Important clinical differences between these patient groups and the immunogenetic heterogeneity support the notion of different antibody-defined scleroderma subsets.     

抗核抗体的研究进展

自身抗体是指抗自身细胞内、细胞表面和细胞外抗原的免疫球蛋白,是自身免疫和自身免疫性疾病重要特征之一。抗核抗体是指抗细胞内所有抗原成分的自身抗体的总称,某些自身免疫性疾病伴有特征性的自身抗体谱,而疾病标记性抗体或特异性抗体可诊断和鉴别诊断疾病特性。自身抗体可判断疾病的活动性及预后,观察治疗反应,指导临床治疗。进一步的抗核抗体谱研究,可阐明抗核抗体与自身免疫性疾病的相关性。该文对抗核抗体谱及其靶抗原与疾病的相关性进行了综述。     

Histone reactivity of drug-induced antinuclear antibodies

Anti-histone antibodies were measured in a group of patients with drug-induced lupus erythematosus and in asymptomatic patients with drug-induced antinuclear antibodies (DANA). Anti-histone antibodies were found in the majority of drug-induced lupus patients. DANA patients had lower titers of ANA and no detectable anti-histone activity. Longitudinal studies of the drug-induced lupus patients showed a gradual fall in the ANA and anti-histone titers. Our data suggest that the immune response in the drug-induced lupus patients is similar to but more intense than that seen in the DANA patients. Possible factors altering the immune response in these 2 groups are discussed.     

Studies of antinuclear antibodies in rheumatoid arthritis

Antinuclear antibodies (ANA) by the indirect immunofluorescence method and their immunospecificities were investigated in 60 patients with rheumatoid arthritis using HEp-2 cells as substrates. ANA were detected in 35% of the patients. The patterns of nuclear staining observed included: diffuse or patchy homogeneous (20%), speckled (8.3%), centromere (3.3%), nucleolar (1.6%) and in 1 patient a mixed pattern (1.6%). The presence of antihistone antibodies (20%) correlated with the presence of an homogeneous pattern on the HEp-2 cells.