Biomedical subjects

A G Sjoholm

Publications and source records attributed to A G Sjoholm.

3 recordsLinked to original sources

PubMed2000

Hic, a novel surface protein of Streptococcus pneumoniae that interferes with complement function.

The important human pathogen Streptococcus pneumoniae was found to absorb factor H, an inhibitor of complement, from human plasma. We identified the gene encoding a novel surface protein, factor H-binding inhibitor of complement (Hic), in the pspC locus of type 3 pneumococci. Unlike PspC proteins in other serotypes, Hic is anchored to the cell wall by means of an LPXTG motif, and the overall sequence homology to various PspC proteins is low. However, the NH(2)-terminal region showed significant homology to the NH(2)-terminal region of several PspC proteins. A fragment of Hic, covering this homologous region, was expressed as a glutathione S-transferase (GST) fusion protein. GST:Hic(39-261) bound radiolabeled factor H and inhibited binding of factor H to pneumococci of different serotypes. Interaction kinetics between GST:Hic(39-261) and factor H were studied with surface plasmon resonance and showed a high affinity binding (K(A) = 5 x 10(7), K(D) = 2.3 x 10(-)(8)). Mutant pneumococci lacking Hic showed no absorption of factor H in human plasma and no binding of radiolabeled factor H, suggesting that Hic is responsible for factor H-binding in type 3 pneumococci. Factor H-dependent inhibition of the alternative pathway was not diminished by the presence of GST:Hic(39-261). In addition, an intrinsic inhibitory effect of Hic is suggested.

Alleles↗

PubMed1997

Serial analysis of autoantibody responses to the collagen-like region of Clq, collagen type II, and double stranded DNA in patients with systemic lupus erythematosus.

OBJECTIVE: To compare autoantibody responses to the collagen-like region of Clq (ClqCLR) with responses to double stranded DNA (dsDNA) and native rat collagen type II during changes of disease activity in patients with systemic lupus erythematosus (SLE). METHODS: IgG antibodies to ClqCLR, dsDNA, and collagen type II were determined by ELISA in serial samples from 33 patients with SLE with different disease manifestations. Antibodies to dsDNA were also detected with the Crithidia luciliae test. RESULTS: Distinct antibody responses in conjunction with flare were observed, but the markers were more clearly related to clinical groups and to severity of disease than to changes of disease activity. Anti-ClqCLR antibodies were detected in 2/10 patients with mild flares, 7/12 patients with severe extrarenal flares, and in 10/11 of the patients with active lupus glomerulonephritis. Findings with regard to anti-dsDNA antibodies were similar. Antibody responses to collagen type II were detected in 7/12 of the patients with severe extrarenal disease, and were less frequently found in the other patients. ELISA absorption and elution experiments with anti-ClqCLR antibodies in the patient sera did not suggest cross reactivity with collagen type II and dsDNA. CONCLUSION: Serial investigation of 33 patients with SLE showed that antibodies to ClqCLR and dsDNA are markers of severe SLE, particularly SLE with kidney involvement. Antibodies to collagen type II are possible markers of severe extrarenal SLE with vasculitis and serositis. Analysis of anti-ClqCLR antibodies provided no evidence of cross reactivity with collagen type II and dsDNA.

Antibodies, Antinuclear↗

PubMed1980

Complement activation, circulating C1q binding substances and inflammatory activity in rheumatoid arthritis: relations and changes on suppression of inflammation.

Patients with rheumatoid arthritis were treated with podophyllotoxin derivatives (PTD) or with cyclophosphamide. Increased concentrations of C1r-C1s-C1 inactivator complexes (C1r-C1s-C1 IA) in serum provided evidence for C1 activation, which was most pronounced before treatment. During treatment the levels of C1r-C1s-C1 IA clearly decreased, while the levels of C4 increased. This rise in C4 was contrasted to the decrease in other acute phase reactants as C-reactive protein. Circulating immune complexes were assessed by the C1q deviation test (C1q DV) and the C1 binding assay (C1q BA). Discrepancies were noted in the outcome of the two assays. Of parameters reflecting C1 inactivation C1r-C1s-C1 IA complexes were positively and C4 negatively correlated with the inflammatory activity as measured by synovitis index (SI). The values in C1q DV correlated with the C1r-C1s-C1 IA values and with SI. In contrast, C1q BA correlated with CRP but not with C1r-C1s-C1 IA or SI. The study gave evidence for a relationship between C1 activation as detected in serum and the extent of synovial inflammation in RA. The possibility is discussed that substances other than immune complexes may be involved in C1 activation and contribute to the synovial inflammation.

Adult↗