PubMed HealthSearch

Biomedical subjects

P Kurki

Publications and source records attributed to P Kurki.

At least 19 recordsLinked to original sources

Maternal HLA antigens and antibodies to SS-A/Ro and SS-B/La. Comparison with systemic lupus erythematosus and primary Sjögren's syndrome.

To study the maternal immunogenetics in congenital heart block (CHB), 31 mothers of affected children were HLA typed for class I and II antigens, and the results were compared with the corresponding HLA types in 900 healthy controls, in 45 mothers with systemic lupus erythematosus (SLE) and in 21 mothers with primary SS who had healthy children. An enzyme-linked immunosorbent assay was used to study the autoantibody responses to the recombinant 52 and 60 kDa SS-A/Ro, and 48 kDa SS-B/La proteins, and to the affinity-purified SS-A/Ro and SS-B/La antigens. Mothers of children with CHB had HLA B8 and DR3 significantly more often than healthy controls [71 vs 10%; relative risk (RR) 9.8, P < 0.00001 and 74 vs 23%; RR9.8, P < 0.001, respectively]. HLA B35 was protective (RR 0.1, P = 0.0029). Compared to controls with SLE, mothers of children with CHB were more often HLA DR3 and DQ2 positive (RR 4.1, P = 0.0057 and RR 3.1, P = 0.031, respectively), and compared to controls with primary SS less often HLA B15 positive (RR 0.1, P = 0.010). In general, the HLA antigen profile in mothers of children with CHB was more closely related to primary SS than to SLE. Levels of antibodies to all three SS-A/Ro antigens were significantly higher in mothers of children with CHB than in controls with SLE and primary SS (P = 0.0001-0.0014). With regard to SS-B/La, the autoantibody responses were similar (P = 0.32-0.66).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Marker antibodies of rheumatoid arthritis: diagnostic and pathogenetic implications.

Rheumatoid arthritis (RA) is associated with several autoantibodies specific enough to serve as diagnostic and prognostic markers. These include rheumatoid factor (RF), antikeratin antibody (AKA), antiperinuclear factor (APF), and anti-RA33. The first three, and possibly also anti-RA33, may precede the onset of clinical RA. The prevalence of positive test reactions depends on the period between taking the specimen and onset of disease; when the period is short, the prevalence is nearly the same as in established disease. Thus, RA has a long asymptomatic period with broadening immunological activity. The assays for AKA and APF (and possibly also for anti-RA33), compared with RF testing, yielded greater specificity rather than the ability to define any subgroup with particularly severe disease. Used together, the above marker antibodies may form a new and more enlightened basis for defining seropositive RA. It is commonly believed that genetically mediated immune response plays an important role in the initiation of RA. However, the role of the major histocompatibility complex antigens may be in modulation of the inflammatory reaction in a later phase.

Antibodies, Antinuclear

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

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

Cell proliferation and expression of cytokeratin filaments in F9 embryonal carcinoma cells.

A double immunofluorescence method was developed for the monitoring of proliferation and differentiation of F9 embryonal carcinoma cells. Cytokeratin filament expression was used as a marker for differentiation, and proliferating cell nuclear antigen (PCNA)/cyclin or bromodeoxyuridine labeling were used as markers for proliferation. F9 cells had a high proliferation rate and were cytokeratin-filament-negative. Upon treatment with retinoic acid and dibutyryl cyclic AMP, cytokeratin-filament-positive cells with differentiated phenotype appeared. After 3 days, the extent of proliferation of cytokeratin-filament-positive cells was comparable to, but after 5 days significantly lower than, that of cytokeratin-filament-negative cells in the same culture. In differentiating F9 cells, cytokeratin filament expression is associated with, and even slightly precedes, the dramatic decrease in the rate of proliferation.

Actin Cytoskeleton

Monoclonal antibodies to proliferating cell nuclear antigen (PCNA)/cyclin as probes for proliferating cells by immunofluorescence microscopy and flow cytometry.

Proliferating cell nuclear antigen (PCNA)/cyclin is an intranuclear polypeptide antigen that is found in both normal and transformed proliferating cells. We have recently described two mouse monoclonal antibodies reacting with PCNA. In this report we describe the application of these antibodies to the study of proliferating human cells by indirect immunofluorescence microscopy and by flow cytometry. A fixation/permeation procedure was developed in order to obtain satisfactory binding of monoclonal PCNA-specific antibodies to proliferating cells. This method involved fixation with 1% paraformaldehyde followed by methanol treatment. For the staining of cells in suspension with the IgM type monoclonal antibodies lysolecithin was added to the paraformaldehyde solution to achieve a better permeation by the antibody molecules. This procedure gave a good ratio of specific staining relative to the background staining. It also preserved the shape and normal architecture of the cells as judged by visual microscopic observation and by light scatter measurements using a flow cytometer. Furthermore, this fixation technique permits simultaneous labeling of DNA by propidium iodide and PCNA by monoclonal antibodies. PCNA was detected in various types of normal and transformed proliferating cells by indirect immunofluorescence. Quiescent peripheral blood mononuclear cells were PCNA-negative whereas a fraction of lectin-stimulated lymphocytes became PCNA-positive. Similarly, early passages of fetal skin fibroblasts were PCNA-positive but non-proliferating senescent fibroblasts of later passages were PCNA-negative. The association of PCNA-staining by monoclonal antibodies with cell proliferation was confirmed by flow cytometry. Simultaneous labeling of PCNA and DNA showed that the PCNA signal increased during the G1 phase of the cell cycle, reached its maximum in the S-phase, and declined during the G2/M phase. Using cell sorting we demonstrated that mitotic cells had a very low PCNA signal. Thus, monoclonal PCNA-specific antibodies offer a convenient tool for the detection of human cell proliferation by immunofluorescence microscopy and by flow cytometry.

Animals

Autoantibody activity of cryoglobulins and sera in systemic lupus erythematosus. Association of IgM class rheumatoid factors with Raynaud's syndrome.

A total of 218 samples obtained during a follow-up study of 36 patients with systemic lupus erythematosus (SLE) were tested for the presence of cryoglobulins. Cold-insoluble precipitates were found in 81% for the patients (29 patients, 114 samples). The protein concentration of the cryoglobulins correlated significantly with the disease activity. Autoantibody activity was determined in the dissolved cryoglobulins and in corresponding serum samples by enzyme-linked immunosorbent assays (ELISA). IgM-RF could be demonstrated more often in the cryoglobulins than in the sera (75% vs. 14%), whereas IgA-RF were seen in 28% of both cryoglobulins and sera. Anti-ssDNA and anti-poly(A) antibodies of both IgG and IgM classes were found more often in the sera than in the corresponding cryoprecipitates. In 7 samples from 5 patients an increase in the IgG-anti-ssDNA activity was seen after DNase digestion of the cryoglobulins. Patients with Raynaud's syndrome had a significantly higher level of cryoprecipitating IgM class rheumatoid factors than other patients. There was also an association between the IgG-anti-poly(A) antibody levels in the cryoglobulins and the activity of the disease. There was no difference with regard to the composition of the cryoglobulins, between patients with nephritis and those without an overt renal disease. Thus, the presence of cryoglobulins in SLE indicates active disease, but not necessarily renal involvement. IgM rheumatoid factors may play a role in the pathogenesis of Raynaud's syndrome of SLE patients.

Adult