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Biomedical subjects

P Kurki

Publications and source records attributed to P Kurki.

At least 37 records · Page 2Linked to original sources

Increased expression of VLA-5 adhesion molecules on synovial fluid T lymphocytes in chronic polyarthritis: a consequence of T-cell activation.

This study focuses on the consequences of T-lymphocyte activation in chronic polyarthritis in terms of expression of cell surface receptors interacting with extracellular matrix (ECM). The expression of the VLA group of integrins was studied on in vitro-stimulated peripheral-blood T cells, and on peripheral-blood and synovial-fluid mononuclear cells (MNC) of patients with polyarthritis. The VLA expression was measured by flow cytometry using monoclonal antibodies (MoAbs) against alpha-subunits of the VLA family. VLA-alpha 4 and VLA-alpha 5, but not VLA-alpha 1, were expressed on a major fraction of unstimulated peripheral-blood T cells both in the patients with polyarthritis and in healthy individuals. Two distinct populations, VLA-alpha 5-high and VLA-alpha 5-low, were found in resting peripheral-blood T lymphocytes. Two days after stimulation by phorbol 12-myristate 13-acetate (PMA) and concanavalin A, most T cells became VLA-alpha 5-high. In patients with chronic polyarthritis, the expression of VLA-alpha 1 and VLA-alpha 5 was always higher on synovial-fluid T cells than on peripheral-blood T cells. These results give further support to the hypothesis that upon activation the induction of the VLA adhesion-molecule expression may be a factor contributing to the accumulation of T cells in the inflamed synovium.

Adult↗

Isolated congenital heart block. Long-term outcome of mothers and characterization of the immune response to SS-A/Ro and to SS-B/La.

OBJECTIVE: To study the long-term outcome of mothers of children with isolated congenital heart block (CHB) and to characterize the maternal autoantibody response to SS-A/Ro and SS-B/La. METHODS: A retrospective clinical study of 33 mothers a mean of 11.2 years (SD 9.2 years, range 0-32 years) after the delivery of their first child with CHB. A clinical and immunologic study of 31 of these mothers, compared with 89 healthy mothers, 45 mothers with systemic lupus erythematosus (SLE), and 19 mothers with primary Sjögren's syndrome (SS), all of whom had healthy children. The specificity of the autoantibody responses to SS-A/Ro and SS-B/La was studied by enzyme-linked immunosorbent assays using purified human recombinant antigens and affinity-purified antigens. RESULTS: By the time of the analysis, 2 (6%) of the 33 mothers of CHB children had died and 6 (18%) had met the criteria for SLE. As a group, mothers of CHB children had clinical and immunologic characteristics more closely related to primary SS than to SLE or any other connective tissue disease. The predominant autoantibody response was to the SS-A/Ro antigens, notably to the 52-kd SS-A/Ro protein (prevalence 97%). Compared with controls with SLE, mothers of CHB children had higher titers of antibodies to recombinant 52-kd and 60-kd SS-A/Ro proteins and to the affinity-purified SS-A/Ro antigen (P < 0.05, P < 0.01, and P < 0.001, respectively). Compared with controls with primary SS, the autoantibody responses were similar. CONCLUSION: The predominant autoimmune disorder in mothers of children with CHB is subclinical primary SS. Antibodies to SS-A/Ro appear to be a prerequisite for the development of CHB.

Adolescent↗

Congenital heart block in one of the HLA identical twins.

A case of HLA identical twins with one affected by congenital heart block is reported. Both twins, as their mother, had more than 12-fold higher anti-Ro antibody titers compared to healthy controls, but no differences were observed between the affected and the healthy baby. It is possible that there is a third factor causing the manifestation of this disease.

Adult↗

Intravenous immunoglobulin treatment of pregnant patients with recurrent pregnancy losses associated with antiphospholipid antibodies.

The effects of high dose iv-immunoglobulin on antiphospholipid antibody levels and on pregnancy outcome was studied in one patient with secondary (SLE) and two patients with primary antiphospholipid syndrome during their four pregnancies. These three women had had two pulmonary embolies related to pregnancy and estrogen containing pills, 13 miscarriages and only one liveborn after pre-eclamptic pregnancy. During the four pregnancies the patients also received 75 mg of aspirin per day. Progressive depression of IgG-anticardiolipin antibody titer was observed after repetitive high dose iv-immunoglobulin (1 g/kg body-weight) infusions. The effects on lupus anticoagulant were variable. Three pregnancies ended in a delivery of healthy child after 36-38 weeks of gestation and one preterm child (34 weeks), with slight respiratory distress syndrome, was born. Our results support the idea that the addition of iv-immunoglobulin to aspirin prophylaxis is worth considering when the patient has a severe antiphospholipid syndrome and/or is refractory to usual treatments.

Abortion, Spontaneous↗

Prospect for an additional laboratory criterion for rheumatoid arthritis.

The aim of the study was to establish the benefit of an additional hypothetical laboratory criterion for rheumatoid arthritis (RA), comprising positivity for antikeratin antibody (AKA) and/or antiperinuclear factor (APF). The tests were applied to a series of 308 hospital patients with various recent-onset inflammatory joint diseases who were followed for 3 years. The performance of APF and AKA was compared with rheumatoid factor (RF). The most sensitive (.72) but the least specific (.86) test for RA was the latex test. The most specific (.96) but the least sensitive (.33) test was AKA. Waaler-Rose and APF were intermediate. AKA and/or APF positive patients had significantly more erosions than patients negative for these autoantibodies. Despite the impressive performance characteristics of APF and AKA, the actual classification impact achieved, as compared to using RF as the sole laboratory criterion, turned out to be moderate. This is because the criteria proved to be interrelated. Unlike RF, AKA and APF are not suited to the general laboratory, at least not in their present form. Moreover they so far lack the broad data base of RF.

Antibodies↗

Antikeratin antibody and antiperinuclear factor as markers for subclinical rheumatoid disease process.

OBJECTIVE: Antikeratin antibody (AKA) and antiperinuclear factor (APF) are antibodies characteristic for rheumatoid arthritis (RA). Our purpose was to obtain information on the occurrence of APF before the onset of clinical disease and on the occurrence of AKA and APF in cases with false-positive rheumatoid factor (RF) reactions. METHODS: AKA and APF were measured with indirect immunofluorescence technique using rat esophagus and buccal mucosa cells, respectively, as antigen source. RESULTS: Five of 30 preillness specimens from subjects who later developed seropositive RA were positive for AKA and APF, 3 sera were positive for only AKA and 3 for only APF. All the eleven sera positive for AKA or APF were RF positive. Both AKA and APF were detected in 6 of 70 sera from RF positive subjects who did not develop RA within a 10-year followup, 3 sera were positive for only AKA and 3 for only APF. CONCLUSION: AKA and APF appear to be linked markers of an immunological process which, in RF positive subjects, predicts the development of clinical arthritis. However, disease manifestations develop in only a proportion of cases.

Adult↗

Cyclosporin A in rheumatoid arthritis--future perspectives.

The new programme for the use of cyclosporin A (CyA) in RA is based on the hypothesis that the drug is more efficacious and better tolerated in early RA and that it can be used as part of therapy with a rational combination of drugs. This paper gives some examples of the ongoing and planned studies that have been set up to test that hypothesis. The development of CyA therapy of RA is a stepwise process. The next steps depend on the outcome of current trials and also on our ability to identify progressive RA at a very early stage.

Arthritis, Rheumatoid↗

Immunopathology of rheumatoid arthritis. Antikeratin antibodies precede the clinical disease.

OBJECTIVE: We sought to determine whether circulating antikeratin antibodies (AKA) precede the onset of rheumatoid arthritis (RA). METHODS: By matching the registers of 2 previous population studies with the registry of patients receiving antirheumatic drugs several years later, pre-illness serum specimens could be obtained from 39 individuals who subsequently developed RA. AKA were assayed with the standard indirect immunofluorescence technique. RESULTS: Ten of 39 serum specimens from individuals who subsequently developed seropositive RA, and 1 of 15 sera from individuals who developed seronegative RA, were positive for IgG-class AKA by immunofluorescence assay. The AKA-positive sera were also positive for rheumatoid factors. CONCLUSION: The findings focus attention on the role of pre-illness immunologic events in the pathogenesis of RA.

Antibodies↗

Antibodies to retroviral proteins in autoimmune connective tissue disease. Relation to clinical manifestations and ribonucleoprotein autoantibodies.

OBJECTIVE: To study the relationship between antibodies that recognize human retroviral proteins and the presence of clinical features and ribonucleoprotein antibodies in patients with autoimmune connective tissue diseases (CTDs). METHODS: Antibodies against native human immunodeficiency virus type 1 (HIV-1) and human T cell leukemia/lymphoma virus type I, recombinant HIV-1 Nef protein, and ribonucleoprotein antigens were determined by immunoblot of sera from 65 prospectively studied patients with definite or suspected CTDs of autoimmune type. RESULTS: Antibodies to retroviral proteins (ARP), most frequently to HIV Gag proteins p55 and p24, were found in 64% of 22 patients with systemic lupus erythematosus (SLE), in 63% of 8 patients with discoid LE (DLE), in 75% of 8 patients with mixed connective tissue disease (MCTD), and in 26% of 19 individuals with chronic biologically false-positive (CBFP) seroreactions, but not in 8 patients with subacute cutaneous lupus erythematosus. No clear correlation of ARP with antibodies to any specific small nuclear RNP antigen was observed. The most striking finding was that recurrent infections, both in LE patients and in those with CBFP reactions and widespread, acral discoid skin lesions, occurred significantly more often in ARP-positive patients. CONCLUSION: The occurrence of antibodies reacting with human retroviral proteins is associated with severe skin lesions and recurrent infections in SLE, DLE, and MCTD patients, and with a disposition toward developing systemic disease in CBFP reactors.

Adolescent↗

Antikeratin antibodies: diagnostic and prognostic markers for early rheumatoid arthritis.

Antibodies to the stratum corneum of rat oesophagus (antikeratin antibodies) were assayed by indirect immunofluorescence in a prospective study of patients with early rheumatoid arthritis (RA). At the beginning of the study, antikeratin antibodies of IgG class were detected in serum samples from 27/71 (38%) patients compared with 1/20 (5%) control patients with reactive arthritis, and 1/38 (3%) healthy blood donors. At the end of the two year follow up, 27/67 (40%) patients with RA were positive for antikeratin antibodies. The patients with RA who were initially positive for antikeratin antibodies had a more active disease course than the patients negative for antikeratin antibodies as measured by clinical, laboratory, and radiological variables. The prevalence of positivity for antikeratin antibodies fluctuated during the follow up, the variation paralleling the disease activity. The occurrence of HLA-DR4 was similar in patients with RA who were positive and negative for antikeratin antibodies. Antikeratin antibodies were also found in seronegative patients with RA, confirming that antikeratin antibodies do not have rheumatoid factor activity. These results show that antikeratin antibodies are detectable at the time of the initial diagnosis of RA and that the positivity for antikeratin antibodies may have prognostic significance in early RA.

Adult↗

Serum hyaluronate level as a predictor of radiologic progression in early rheumatoid arthritis.

Increased serum levels of hyaluronate (HA) have been found in patients with rheumatoid arthritis (RA). This probably reflects increased leakage of HA from the inflamed joints into the circulation. In a prospective study of 40 patients with early RA, we evaluated the relationship of serum HA to clinical, laboratory, and radiologic parameters of disease activity. The patients were followed for 12 months; all had active disease at study entry. We confirmed the previous finding of higher serum HA concentrations in RA patients compared with healthy controls. At study entry, the patients' serum HA levels correlated positively with clinical and laboratory parameters of acute inflammation. Despite marked clinical improvement during therapy with second-line drugs, the serum HA levels increased during the followup period. At the end of 1 year, these levels correlated with the radiologic progression of joint lesions, whereas they showed a less pronounced correlation with clinical or laboratory parameters of inflammation. We conclude that, in early RA, serum HA levels may reflect ongoing joint destruction and may even predict subsequent joint damage.

Adult↗

Congenital heart block: successful prophylactic treatment with intravenous gamma globulin and corticosteroid therapy.

In mothers with anti-Ro-positive antibodies whose previous pregnancies have ended in deliveries of infants with congenital heart block, prophylactic therapeutic strategies are used to try to diminish the production and passage into fetal circulation of autoantibodies. Intravenous gamma globulin was given at 14 and 18 weeks' gestation and prednisone was given from 14 weeks' gestation to a woman with Sjögren's syndrome. The pregnancy ended with delivery of an infant without congenital heart block.

Adult↗

Cellular fibronectin in rheumatoid synovium and synovial fluid: a possible factor contributing to lymphocytic infiltration.

Mouse monoclonal antibodies against ED sequence-containing cellular fibronectin (cFn) were used to show that Fn in the inflamed synovium is distinct from the major form of plasma Fn (pFn). An accumulation of cFn was seen at sites of hyperplasia of the rheumatoid synovial membrane and in the walls of small vessels in the synovium by immunofluorescence microscopy. cFn was also found in rheumatoid synovial fluid by immunoblotting. Approximately one-fifth of the T lymphocytes from rheumatoid synovial fluid bound to Fn. The binding of synovial fluid T cells was always higher than that from peripheral blood. These results have two implications. On the one hand, the cellular type of Fn may be an indicator of synovial inflammation. On the other hand, the deposition of Fn may be a factor contributing to the infiltration of mononuclear cells into the synovium.

Animals↗

Desmin antibodies in acute infectious myopericarditis.

The role of autoantibodies against cardiac tissue in the pathogenesis of acute myopericarditis is poorly understood--partly because the specificity of the antibodies is unknown. We assayed antibodies against desmin, a cytoskeletal muscle protein, in 18 patients with acute infectious myopericarditis (AIM), in 24 patients with acute uncomplicated infections, in ten patients with acute myocardial infarction, and in 68 blood donors by an immunoenzymatic assay using purified desmin from Purkinje fibers of cow heart. In addition, anti-heart antibodies were assayed by indirect immunofluorescence. Anti-heart antibodies were detected in all groups by indirect immunofluorescence. On the other hand, anti-desmin antibody levels exceeding the mean + 2 SD of the blood donors could demonstrated in seven (39%) AIM patients but in only one patient in the other groups. The analysis of serial samples indicated that the antibody level was highest in the acute phase of AIM and declined during the recovery.

Acute Disease↗