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D Isenberg

Publications and source records attributed to D Isenberg.

At least 73 records · Page 4Linked to original sources
PubMed1993

Identification of the 9G4 idiotope in systemic lupus erythematosus.

An idiotope designated 9G4 (9G4Id) is known to be a marker for immunoglobulins which utilize a particular VH gene, VH4-21. The idiotope has been found to be present on anti-DNA antibodies, and have been identified in 45% of sera from patients with SLE. This idiotope is strongly associated with lupus being very uncommon amongst the other autoimmune rheumatic diseases tested. This distinction is unlike virtually any of the other DNA antibody idiotypes described which are much more widely distributed. 9G4Id levels were found to fluctuate with disease activity in some lupus patients and this idiotope was detected in 3/11 SLE renal biopsies tested. Its presence is associated with the HLA markers A1 and B8 and raised 9G4Id levels are not simply a reflection of hypergammaglobulinaemia. Thus a new DNA antibody associated idiotope has been identified. Expression of the idiotope indicates that a notable proportion of anti-DNA antibodies have VH segments encoded by the same, or closely related genes, and that these restricted immunoglobulins are involved in the renal pathology found in SLE.

Humans↗
PubMed1993

The differential expression of heat shock proteins in rheumatic disease.

The concept of overexpression of endogenous heat shock proteins (hsps) is central to hypotheses in which hsps are implicated in the pathogenesis of autoimmune rheumatic disease. Hsps were quantitated in protein samples prepared from peripheral blood mononuclear cells (PBMC) of patients and controls by Western blotting and scanning densitometry. Evidence is presented for a specific pattern of overexpression of the 90 kDa hsp (hsp 90) and the highly inducible member of the 70 kDa hsp family (hsp 72) occurring overall in SLE relative to other diseases. Evidence is also presented for the differential expression of individual hsps in other autoimmune rheumatic diseases such as RA, primary SS and systemic sclerosis, and in other relevant conditions such as infectious diseases and multiple sclerosis. It is concluded that, while hsp 90 overexpression may have a specific role in, for example, SLE, overexpression of hsp 72 and underexpression of the constitutive member of the hsp 70 family (hsp 73) may be a more general reflection of ongoing disease states.

Adolescent↗
PubMed1993

Rheumatoid factor: primary or secondary event in the pathogenesis of RA?

Rheumatoid factors have been recognised and studied for over fifty years. They are anti-IgG immunoglobulins which occur in most patients with rheumatoid arthritis. Their precise contribution to the pathology of this disease however remains an enigma, since they are also demonstrable in other autoimmune and infectious diseases, as well as in normal healthy controls. Thus the importance of RF in RA may not pertain merely to their presence, but to the nature of the autoantibodies themselves. RF in RA are found to differ from those in control subjects and in other diseases such Waldenstrom's macroglobulinaemia in terms of their binding affinities for IgG, subclass specificity and V gene usage. The role of RF as either the initiating factor or its occurrence as a secondary event in RA is discussed.

Arthritis, Rheumatoid↗
PubMed1993

Lymphocyte subsets in a large cohort of patients with systemic lupus erythematosus.

In search of markers of disease activity in patients with SLE we have investigated blood lymphocyte subsets from a large cohort of patient. Seventy-one patients were studied using a well-defined panel of fluorescent monoclonal antibodies which recognize the major T, B and NK lymphocyte subsets and activated cells. Flow cytometry was used with standard automated software. Overall, SLE patients were lymphopenic. The proportion of activated T cells was increased and NK cells were decreased in both proportion and absolute numbers (P < 0.001). This decrease was more pronounced in the more active patients. None of the T cell activation markers was shown to distinguish different degrees of disease activity. However, the percentage of NK cells was significantly reduced in active disease states (P < 0.01). Decreased numbers of NK cells could potentially reduce the resistance of SLE patients to infectious organisms.

Adult↗
PubMed1992

Transcription of the genes encoding the small heat shock protein ubiquitin is unchanged in patients with systemic lupus erythematosus.

The heat shock proteins hsp90 and hsp70 have been shown to be over-expressed in peripheral blood mononuclear cells from SLE patients. We show, however, that transcription of the three genes encoding the small hsp ubiquitin is not enhanced in these patients. The over expression of hsp90 and hsp70 in SLE is likely therefore to reflect cellular events resulting in the specific induction of these hsps rather than a generalized induction of all hsp synthesis due to the stress of the disease or the presence of fever.

Gene Expression↗
PubMed1992

Production of human monoclonal antibodies to myeloperoxidase.

Two mouse-human heterohybridomas secreting human antibodies to myeloperoxidase (MPO) were derived from the peripheral blood of a patient who developed microscopic polyarteritis as the result of long-term treatment with hydralazine. Forty-five immunoglobulin-secreting lines were obtained from the fusion of patient lymphocytes with the CB-F7 heteromyeloma cell line. Of these, two antibodies, one IgG and one IgM, bound to myeloperoxidase in solid phase ELISA and gave a perinuclear staining pattern on ethanol-fixed human neutrophil cytospin preparations. The staining patterns were similar to those seen with serum from the patient. Antigen-inhibition studies revealed that the affinity of the IgG monoclonal antibody was 28 times higher (k = 1.4 x 10(-7)) than the IgM antibody (k = 5 x 10(-5)). Cross-inhibition studies further suggested that the two monoclonal antibodies recognized the same epitope on MPO. Of the other secreting cell lines, none produced antibody which reacted with the panel of autoantigens used for testing. Neither mononuclear antibody reacted with this panel indicating that they were not simply polyreactive natural autoantibodies. These are the first human monoclonal antibodies to native myeloperoxidase to be reported.

Animals↗
PubMed1992

Crosscultural validation and reliability of 3 disease activity indices in systemic lupus erythematosus.

Rheumatologists from 4 countries, representing 8 rheumatology centers, tested 3 systemic lupus erythematosus (SLE) disease activity indices: the SLE Disease Activity Index (SLEDAI) from Toronto; the Systemic Lupus Activity Measure (SLAM) from Boston and the British Isles Lupus Assessment Group (BILAG) for their reproducibility and validity in the assessment of real patients. Seven patients representing a spectrum of disease manifestations and activity were each examined by 4 of 7 observers from all centers except Toronto, using a Youden square design. Each observer completed all 3 indices and a category rating scale for disease activity on each of the 4 patients seen. All 3 indices detected differences among patients. There was no detectable observer effect among the 7 observers with each of the 3 indices. There was a detectable order effect with the SLAM. The 3 indices are comparable and reproducible for evaluating disease activity in SLE.

Boston↗
PubMed1991

Agalactosyl IgG: an aid to differential diagnosis in early synovitis.

Sixty consecutive patients presenting with early-onset synovitis were studied by measuring rheumatoid factor (RF) titers and the percentage of oligosaccharide chains attached to the C gamma 2 domain of IgG that lack galactose (GAL[0]). After 2 years of followup, 39 patients (65%) had developed rheumatoid arthritis (RA), and 21 had developed a variety of other inflammatory joint diseases. A combination of RF positivity and GAL(0) levels above the age-corrected mean gave a positive predictive value for a diagnosis of RA in 94% of these patients. These observations may well have clinical utility.

Adult↗
PubMed1991

Changes in IgG glycoform levels are associated with remission of arthritis during pregnancy.

It was found that the percentage of IgG-associated agalactosyl N-linked oligosaccharides (G0) falls during normal human pregnancy and rises to values higher than before conception following delivery (n = 10, 39-55 days after delivery). Serial bleeds from a normal pregnant woman showed a fall in the percentage G0 during gestation and a rapid rise post-partum. A similar study on a pregnant arthritic woman with a pathologically elevated percentage G0 also showed a fall in percentage G0 during pregnancy and a rapid rise post-partum. The changes in IgG glycosylation in the pregnant arthritic woman occurred simultaneously with the pregnancy-induced remission and post-partum recurrence of disease. A further seven pregnant women with rheumatoid arthritis were studied and analysis of their G0 values pre- and post-partum confirmed the result. In a further series of experiments using an animal model of rheumatoid arthritis, DBA/1 mice with collagen-induced arthritis were found to have elevated G0 levels compared with control mice. The percentage G0 was found to fall simultaneously with pregnancy-induced remission to the same value as non-arthritic pregnant mice. Post-partum recurrence of arthritis in these mice was also accompanied by a simultaneous and rapid rise in percentage G0. Pseudopregnancy did not result in a change in the percentage G0, confirming the effect of true pregnancy. Since the proportion of agalactosyl IgG is abnormally high in the serum of patients with rheumatoid arthritis these changes in IgG glycoform levels, or the factors which control them, may be related to the mechanisms underlying remission of arthritis in humans during pregnancy.

Acetylglucosamine↗
PubMed1991

Autoimmunity associated with infection: leprosy, acute rheumatic fever and Lyme disease.

This review examines the links between autoimmunity and three common infectious diseases. These disorders are associated with a variety of clinical and serological autoimmune phenomena. In addition they might conceivably trigger autoimmune diseases themselves. Mechanisms that may be responsible for these links, including molecular mimicry, are explored.

Acute Disease↗
PubMed1991

Insidious loss of renal function in patients with anticardiolipin antibodies and absence of overt nephritis.

Circulating anticardiolipin antibodies are associated with recurrent thrombosis, fetal loss and thrombocytopenia. We have identified four patients with SLE or lupus-like disease who have high circulating levels of ACLA, repeated thrombosis and evidence of renal disease. Their clinical signs and symptoms of lupus activity were minimal, yet all had renal insufficiency with GFR 50 ml/min or less despite no history nor evidence of overt nephritis (proteinuria less than 0.5 g/day and no haematuria). Renal biopsy specimens showed focal ischaemic lesions with no evidence of active lupus nephritis. We describe a new lesion of renal ischaemia secondary to non-inflammatory vascular pathology associated with circulating ACLA.

Adult↗
PubMed1991

T cell receptor expression in Sjögren's syndrome.

T lymphocytes expressing the gamma/delta T cell receptor and B lymphocytes expressing CD5 are known to occur in expanded numbers in the peripheral blood of patients with primary Sjögren's syndrome. The cellular infiltrates for the surface phenotypic markers for alpha/beta and gamma/delta T cell receptors, CD4, CD8, CD45, and CD5 were examined in lip biopsy specimens from two patients with primary Sjögren's syndrome, six with secondary Sjögren's syndrome, and seven healthy controls. Most of the Sjögren's lip biopsy cellular infiltrates were T lymphocytes of the CD4 subset expressing the alpha/beta T cell receptor (mean 70%). The low prevalence of gamma/delta T cell receptor bearing cells in lip biopsy specimens is maintained in Sjögren's syndrome (mean 1.5%), and thus it seems unlikely that these lymphocytes bearing the gamma/delta T cell receptor have a major role in the immunopathology of Sjögren's syndrome. Over 70% of cells within the lesional infiltrate of primary and secondary Sjögren's syndrome expressed the CD5 and CD45 cell surface molecules.

Antigens, CD↗
PubMed1991

Heat shock proteins and systemic lupus erythematosus.

This review briefly defines the heat shock proteins (hsps), their classification and their functions. The hypothesis that links hsps to the development of autoimmunity is explored, together with the rationale for investigation of the relationship between hsps and systemic lupus erythematosus (SLE). Thus, published work on this subject falls into three main categories: the overexpression of hsps in SLE, the development of autoantibodies to hsps in SLE, and the surface expression of hsps in peripheral blood mononuclear cells in SLE. This work is reviewed in detail. In conclusion, we describe areas for further study and outline ways in which this is being approached.

Autoimmunity↗
PubMed1991

Expression of a common idiotype PR4 in the sera of patients with leprosy.

The sera of 187 patients from across the leprosy spectrum were screened for the expression of the PR4 idiotype, which was first identified on a human hybridoma-derived monoclonal antibody from a patient with leprosy and found to react with the Mycobacterium leprae phenolic glycolipid and a variety of polynucleotides. Sixty per cent (51 out of 85) of patients with lepromatous leprosy (LL), 66% (33 out of 49) with borderline lepromatous (BL) disease, 47% (14 out of 30) with borderline tuberculoid (BT) leprosy, and 56% (13 out of 23) of tuberculoid (TT) patients were found to have significantly elevated titres of the PR4 idiotype in their sera compared with endemic controls, irrespective of the presence or absence of endemic malaria. Sera from 52 patients with tuberculosis were also screened as a control for mycobacterial infection. The PR4 idiotype was significantly elevated in 37% (19 out of 52) of these patients. No correlation between idiotype and serum immunoglobulins IgG and IgM was found, indicating that the concentrations of idiotype levels in sera were not merely a reflection of changes in serum immunoglobulin levels. It is hypothesized that the expression of the PR4 idiotype is due to certain germline genes preferentially expressed rather than being the result of polyclonal B cell activation.

Animals↗