Biomedical subjects
Publications and source records attributed to N Snowden.
A 32-year-old male presented with two episodes of meningococcal septicaemia, each of which was caused by a different serogroup of Neisseria meningitidis. Examination of the alternative pathway of complement revealed the rare X-linked disorder properdin deficiency (PD). Meningococcal Infection in complement deficiency states is discussed and the unusual features of this case are highlighted.
Extra-articular or systemic features occur commonly in seropositive erosive rheumatoid arthritis (RA). Clinical, pathological and immunogenetic evidence suggests that nodule formation, vasculitis and Felty's syndrome can be considered as manifestations of the same fundamental disease process as rheumatoid synovitis. However, while synovitis seems likely to be driven by macrophage activation induced by Th1 cells, systemic involvement in RA is characterised by B cell overactivity, immune complex formation and complement consumption, suggesting that Th2 cells are involved in the pathogenesis of extra-articular rheumatoid disease.
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OBJECTIVE: To assess whether the HLA-DR4 association found in rheumatoid arthritis (RA) is also seen in the large granular lymphocyte (LGL) syndrome. METHODS: HLA-DR genotyping was performed using restriction fragment length polymorphism and polymerase chain reaction analysis. RESULTS: LGL syndrome patients with RA showed the same HLA-DR4 association seen in RA/Felty's syndrome (FS), while LGL syndrome patients without arthritis did not. CONCLUSION: It is proposed that FS and the LGL syndrome represent different variants of a broader syndrome comprising RA, neutropenia, LGL expansions, HLA-DR4 positivity, and splenomegaly.
In humans, the T cell repertoire is influenced by HLA, T cell receptor null alleles and antigen. Here, we describe a novel mechanism, independent of superantigen or T cell receptor structure which influences the T cell repertoire in a V beta-dependent manner. We have identified a biallelic locus, the TCRBV13S2 T cell receptor gene, where allelic differences predominate in the non-coding regions including transitions, transversions and frameshift deletions. The expressed protein is non-polymorphic at this locus. The TCRBV13S2 genotype profoundly influences the circulating levels of V beta 13.2 CD4 T cells but does not affect T cell receptor expression or function.
OBJECTIVES: To determine whether the active 25 kDa form of the fibrogenic cytokine transforming growth factor beta (TGF beta) can be detected in plasma from patients with systemic sclerosis and to examine the relationship between plasma TGF beta and clinical markers of disease severity and serum concentrations of the aminoterminal peptide of type III procollagen (PIIINP) (a laboratory marker of the fibrotic process). METHODS: A cross sectional study was made of 39 patients with systemic sclerosis (11 diffuse and 28 limited), nine patients with primary Raynaud's disease and 60 healthy controls. TGF beta 1 and TGF beta 2 were measured by enzyme linked immunosorbent assay (ELISA) (sensitivity 100 pg/ml) and PIIINP by radioimmunoassay. RESULTS: TGF beta 1 was detected in plasma from six of 39 patients with systemic sclerosis but not in any patient with primary Raynaud's disease or healthy controls. TGF beta 2 was not detected in plasma from patients or controls. No clear relationship was demonstrated between TGF beta 1, clinical features or PIIINP concentrations. CONCLUSIONS: The 25 kDa form of TGF beta 1 can be detected in the plasma of some patients with systemic sclerosis. This provides limited support for the hypothesis that this cytokine plays a role in the pathogenesis of this disease. However, longitudinal studies, particularly in early diffuse disease, are required to clarify the relationship between circulating TGF beta 1 and disease activity.
Serum samples from 149 patients with RA and other rheumatological diseases, and 57 non-arthritic controls have been assayed for IgE antibodies to the cartilage collagen types II, IX and XI in their native and denatured state. Using an improved ELISA technique together with antigen-binding inhibition studies to confirm specificity, 10 of the 149 (7%) patients showed IgE antibodies to human collagen type II and bovine collagen types II, IX or XI. Some patients responded to only one collagen type whereas others had IgE positive responses to two or all three collagen species. Most of the IgE responses detected were directed towards the denatured collagens. Those sera showing an IgE response to bovine type II collagen produced a similar response to the human equivalent, including two patients with SLE. None of 57 control subjects demonstrated IgE specificity for any of the cartilage collagens. Patients with IgE specificity for the cartilage collagens did not demonstrate IgM or IgA specificity for these antigens, but two of these patients showed IgG responses to type II and XI collagens. Whereas eight patients were exclusively IgE-positive for the cartilage collagens, others expressed specificities for IgG, IgM or IgA. It therefore appears that the specific autoimmune profile for each patient is often different from others, both in terms of the class of immunoglobulin expressed and the collagen antigens recognised. At present no correlations were observed between the IgE-positive patients and their clinical assessment and/or prognosis.
Class II major histocompatibility complex (MHC) proteins bind and present peptide antigens to T cells. Moreover, their function as signal transduction molecules has recently been emphasized. Here we used Epstein-Barr virus (EBV)-transformed B-cell lines (B-LCL) in experiments to investigate the changes induced by binding of specific antibodies to HLA-DR molecules. Binding of the antibodies induced, in an allele-specific manner, striking non-cytotoxic inhibition of B-LCL proliferation. This inhibition was associated with an increase in shedding of soluble CD23. These findings provide further evidence for the function of MHC class II proteins as signal transduction molecules which may be important in B-cell activation.
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Thirteen patients with expansion of an unusual subset of T lymphocytes, defined by large size, cytoplasmic granularity and CD3+ CD8+ Leu 7+ surface phenotype, are reported. Although morphologically and/or phenotypically abnormal lymphocytes were found in all patients, only five had an absolute peripheral blood lymphocytosis. Ten patients had a bone marrow lymphocytosis. As in previous series, there was a strong association with neutropenia (12 patients) and polyarthropathy (seven patients). The latter group displayed a wide range of articular disease: classical or definite rheumatoid arthritis in four patients and milder non-erosive disease in the remainder. All 13 patients showed evidence of abnormal B cell function: IgM rheumatoid factor was present in nine patients, neutrophil-specific antibodies in six and all showed an increased level of at least one immunoglobulin isotype. These patients may be difficult to distinguish from those with idiopathic neutropenia and Felty's syndrome. Such a distinction may not be made on clinical grounds alone: critical assessment of lymphocyte morphology, bone marrow examination and analysis of lymphocyte phenotype should be considered in all patients with unexplained neutropenia, particularly in the context of arthritis. It is suggested that the true prevalence of this syndrome may have been greatly underestimated.
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Anticardiolipin antibody levels were measured in 57 patients with Mycoplasma pneumoniae infection and 21 patients with other infections. Significantly more patients in the mycoplasma group had increased IgM and IgG anticardiolipin. Within the mycoplasma group significantly higher titres were found in patients with severe infection (assessed by need for hospital admission) and in patients with cold agglutinins. A tendency for particularly high titres to occur in patients with extra-pulmonary complications was identified.
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This study reports the effects of subinhibitory concentrations of the antibiotics, clindamycin, gentamicin, moxalactam, and penicillin G, against 6 blood isolates of Streptococcus faecalis to determine possible enhancement of phagocytosis. In addition, combinations of penicillin G plus streptomycin, penicillin G and gentamicin, and clindamycin plus gentamicin were studied to determine synergistic growth inhibition. Results suggest no observable effect in phagocytosis from subinhibitory concentrations of the studied antibiotics singly or in combination. The number of viable intracellular Str. faecalis were also not affected by pre-treatment with antibiotics.