Search PubMed⌕ Search

Biomedical subjects

F Oksman

Publications and source records attributed to F Oksman.

At least 37 records · Page 2Linked to original sources
PubMed1994

Golgi autoantibodies and autoantigens.

Autoantibodies directed against cellular constituents rarely react with antigens localized in the Golgi apparatus and little information is available regarding these particular antibodies. Although thousands of samples have been examined for autoantibodies in our laboratory on a routine basis, only three human sera with anti-Golgi antibodies could be studied. Using pre-embedding immunoelectron microscopy we have demonstrated that these sera have antibodies reacting with antigens located in the Golgi apparatus. The reaction product was exclusively located on cisternal and vesicular Golgi membranes. No intraluminal staining was seen and some saccules were negative. No specificity for a peculiar tissue or cell line was noted, suggesting that the targets or these autoantibodies are evolutionarily conserved. The F(ab')2 fragments retained full binding capacity in indirect immunofluorescence experiments, confirming true antibody activity. When tested by immunoblotting, the three sera reacted with different antigens with relative molecular weights of respectively 230, 150 and 80 kDa. The antigens recognized by anti-Golgi antibodies in two of the three sera were insensitive to trypsin degradation. Together, these results suggest that a set of different autoantigens are recognized by sera from various patients.

Animals↗
PubMed1994

Neutrophilic dermatosis: a case of overlapping syndrome with monoclonal antineutrophil cytoplasmic autoantibody activity.

A 66-year-old male patient presented, over a 10-year period, polymorphic cutaneous manifestations with extensive neutrophilic infiltration which supports the diagnosis of overlapping syndrome of neutrophilic dermatoses. This was associated with a benign monoclonal gammopathy of IgA lambda type that had antineutrophil cytoplasmic autoantibody (ANCA) activity. Neutrophilic dermatoses may be associated with or can trigger ANCA.

Aged↗
PubMed1993

Antineutrophil cytoplasm antibodies in systemic polyarteritis nodosa with and without hepatitis B virus infection and Churg-Strauss syndrome--62 patients.

OBJECTIVE: Antibodies directed against components of neutrophil cytoplasm have been detected in various systemic vasculitides and especially in Wegener's granulomatosis. In polyarteritis nodosa (PAN) and Churg-Strauss syndrome, few data are available and correlation between clinical manifestations and antineutrophil cytoplasm antibodies (ANCA) has not been established. Therefore, we tested, before treatment of vasculitis, 62 consecutive patients suffering from PAN with hepatitis B virus (HBV) markers, PAN of unknown etiology or Churg-Strauss syndrome. METHODS: Only patients with PAN and Churg-Strauss syndrome were included in the study. The diseases were histologically and/or angiographically proven. Every patient's serum was tested by an indirect immunofluorescence assay (IFA) and, in 37 cases, by an enzyme linked immunosorbent assay (ELISA). RESULTS: ANCA detected by IFA were observed in 10.7% of the patients with PAN with HBV markers, in 27.3% of the patients with PAN without HBV markers and in 66.7% of the patients with Churg-Strauss syndrome. When ELISA was performed, 11.1% of the patients with PAN associated with HBV infection, 20% of the patients with PAN without HBV markers and 55.6% of the patients with Churg-Strauss syndrome were positive. ANCA were positively correlated with asthma and purpura and negatively correlated with HBV markers. CONCLUSION: Regardless of the technique used, Churg-Strauss syndrome was associated with ANCA in about 60% of the cases while, in PAN of unknown etiology, ANCA were found in about 25% of cases. In contrast, IFA and ELISA only detected ANCA in a limited number of cases of PAN related to HBV infection. ELISA positivity in patients with PAN and Churg-Strauss syndrome was usually associated with antimyeloperoxidase antibodies. In our cases of PAN, ANCA and purpura were significantly correlated, suggesting that, in these cases, small vessels are involved and therefore macroscopic and microscopic PAN coexist. Thus it seems that ANCA are essentially present in the cases of small vessel vasculitis, as has been described, and are not a marker of pure macroscopic PAN, at least at our present level of understanding of these antibodies.

Adult↗
PubMed1993

[Anti-cytoplasm antibodies to polynuclear neutrophils: specificity in renal vasculitis].

We present a retrospective study of all patients with a positive anti-neutrophil cytoplasm autoantibodies (ANCA) result from July 1987 to December 1990. The aims of the study were to assess specificity of ANCA in renal vasculitis and to correlate ANCA immunofluorescence subtypes with clinical aspect, diagnosis, severity and outcome. Anti-myeloperoxidase antibody (A-MPO) was sought in 31 cases. Specificity was 86% and false-positive results were 11%. ANCA subtypes varied with the clinical picture. C-ANCA were more often present when renal vasculitis was associated with pulmonary and ear, nose and throat involvement; P-ANCA were more often present when there was no respiratory tract involvement. Thus C-ANCA were preferentially associated with Wegener's granulomatosis and P-ANCA with microscopic polyarteritis and pauci-immune necrotizing and crescentic glomerulonephritis. No correlation was found between ANCA subtypes and severity or outcome. A-MPO were positive in 14 cases (especially in micropolyarteritis and necrotizing glomerulonephritis).

Autoantibodies↗
PubMed1992

An in vivo model for the experimental selection of drugs able to prevent immune complex glomerulonephritis.

Polyclonal activation of lymphocytes and immune complex-mediated glomerular lesions were induced in C57Bl/6 mice by injecting bacterial lipopolysaccharide (LPS) twice a week for 2 weeks. The usefulness of such a model for in vivo evaluation of immunomodulatory and therapeutic effects of drugs, was investigated by treating mice with DIAM4, a cyclophosphazenic compound known to modulate polyclonal activation of lymphocytes and to prevent mouse lupus nephritis. Prevention of LPS-triggered lymphocyte polyclonal activation and glomerular lesions was observed in the DIAM4-treated mice. Such a model can be used conveniently to select compounds effective in the treatment of immune glomerulonephritis.

Animals↗
PubMed1992

Prevalence of thyroid abnormalities in patients with rheumatoid arthritis.

The prevalence of thyroid abnormalities was determined in 131 patients: group I = rheumatoid arthritis, 68 patients, group II = systemic immunological diseases (IIa Sjögren's syndrome, n = 6; IIb other rheumatic autoimmune disease, n = 17), group III = other rheumatic diseases n = 13 and control group (n = 27). Thyroid abnormalities (hypo, hyperthyroidism, nodular goiter) were frequent: 33.8% in group I, 100% in group IIa, 11.7% in group IIb. Hypothyroidism was present in 19.1% (group I), 50% (group IIa). 6% (group IIb). Autoimmune thyroiditis was found in 16.2% in group I, 100% in group IIa, 11.7% in group III. Thyroid diseases are frequent in patients with rheumatoid arthritis. Therefore thyroid tests might be performed in patients with rheumatoid arthritis.

Aged↗
PubMed1992

[Micropolyarteritis].

Micropolyarteritis are defined as necrotizing inflammatory lesion of the wall of small vessels affecting different organs. A necrotizing crescentic glomerulonephritis without immuno-deposits is observed in the kidney, frequently involved in this microscopic form of systemic vasculitis. Micropolyarteritis are regrouped with Wegener's syndrome and isolated pauci-immune necrotizing crescentic glomerulonephritis as "ANCA-related vasculitis", whose diagnosis is assessed throw renal biopsy and prognosis dependent on immuno-suppressive treatment. Sixty-one patients treated in our nephrology department for a RPGN during these ten recent years have been retrospectively studied. Among them, twenty-five patients presented clinical and morphologic aspects compatible with the diagnosis of micropolyarteritis. We present their clinical aspects and evolution under treatment.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1992

[Anti-polynuclear neutrophil cytoplasmic antibodies of the perinuclear type or p-ANCA].

Some neutrophil cytoplasmic auto-antibodies produce perinuclear immuno staining of alcohol-fixed neutrophils called P-Anca pattern. These autoantibodies show chiefly reactivity with myeloperoxidase in Elisa but other specificities have been detected (elastase, cathepsin, lactoferrin). These P-Anca anti-MPO are more frequent with renal angiitis but P-Anca (anti-MPO negative) are associated with other diseases without renal failure (rheumatoid arthritis, Gougerot-Sjogren and ulceritis colitis).

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1992

[Does bullous pemphigoid with negative direct immunofluorescence exist? Apropos of 3 cases].

Subepidermal autoimmune bullous dermatoses are defined by clinical, histological and immunological criteria, notably the presence of anti-basement membrane antibodies detectable in vivo by direct immunofluorescence. We report three cases where anti-basement membrane antibodies were not detectable in vivo by direct immunofluorescence but were detected in high titres by indirect immunofluorescence. This situation is extremely rare in the literature. The first case concerns a 69-year old woman seen for bullous and pruriginous lesions of the lower limbs of 2 months' duration. Histological examination found dermoepidermal bullae with, in their lumen, a serous fluid spotted with numerous polymorphonuclears. A search for anti-basement membrane antibodies was positive in significant titres (1,280; 320; 480) at indirect immunofluorescence on rabbit lip whereas five successive direct immunofluorescence test in perilesional skin and on the thigh medial surface remained negative. The second case is that of a 91-year old woman suffering from generalized pruritus associated with erythematous lesions predominant on the extension surfaces of the forearms and thighs, without any bullous lesion. Pathological examination only showed a superficial dermal lymphocytic infiltrate. Four direct immunofluorescence tests were negative, whereas a search for anti-basement membrane antibodies on rat oesophagus was positive at 1/1,280. The third case resembles the second one. It concerns a 72-year old woman who consulted for generalized pruritus of several months' duration which interfered with sleep and was incompletely relieved by emollients. There was no specific skin lesion. Pathological examination revealed nothing more than a discrete perivascular mononucleate infiltrate. Direct immunofluorescence tests performed on two occasions on the skin of the abdomen and of the medial thigh surface were negative.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

The beta-blocker acebutolol down modulates the spontaneous polyclonal activation of lymphocytes in NZB X NZW lupus mice.

Acebutolol is a beta blocking agent that induces in C57Bl/6 mice a polyclonal activation of lymphocytes (PAL). In this study, its effect on cellular parameters of spontaneous PAL and lupus disease in NZB x NZW female mice is investigated. A significant reduction of PAL is found in 10-week-old mice after only five injections of 50 mg/kg/day of acebutolol. This effect is also observed in 7- and 9-month-old mice after 12 weeks of treatment. In these chronically treated mice, a significant decrease in incidence and levels of proteinuria as compared with untreated mice is found. No statistically significant increase in survival is observed. In conclusion, acebutolol down modulates the spontaneous PAL which characterizes the NZB x NZW mouse lupus disease and might prevent to some extent the development of nephritis.

Acebutolol↗
PubMed1991

Polyreactivity of human monoclonal antibodies: human anti-Rh monoclonal antibodies of IgM isotype are frequently polyreactive.

The specific aim of this study was to characterize human anti-Rh monoclonal antibodies cross-reacting with self-antigens. We studied supernatants from man-mouse hybridomas and from lymphoblastoid cell lines. Man-mouse hybridomas were established by fusion of peripheral blood lymphocytes from healthy individuals recently immunized against Rh alloantigens, with mouse myeloma (or man-mouse heteromyeloma) cell lines. Lymphoblastoid cell lines were produced by Epstein-Barr virus induction of lymphocytes from identical sources. Of the 55 monoclonal alloantibodies studied, 11 also reacted with intracellular self-antigens as demonstrated by immunofluorescence assay on cryostat sections of human tissues. This cross-reactivity was mainly a property of monoclonal alloantibodies belonging to the IgM isotype (among the 11 cross-reacting mAbs 10 were IgM). The cross-reactivities of these monoclonal antibodies were ascertained by absorption of alloreacting antibodies with red blood cells. Similar results were obtained on a panel of purified cellular antigens by ELISA. The results confirm that during an immune response against a foreign antigen (alloantigen), B cells that produce polyreactive antibodies are not excluded from the pool of responding cells. Therefore, polyreactive autoantibodies present in sera from healthy individuals may be the result of an immune response against foreign antigens.

Antibodies, Monoclonal↗
PubMed1990

Autoantibodies to lamins in rheumatoid arthritis.

The presence of autoantibodies reacting with lamins A and C was demonstrated in sera from 2 patients with rheumatoid arthritis (RA). One patient developed antilamin antibodies several years after being diagnosed as having RA; she was also found to have chronic active hepatitis. The second patient had severe nodular RA. We describe the other serologic findings in these 2 patients and discuss the relationships between antilamin antibodies and RA.

Aged↗
PubMed1989

Human monoclonal autoantibodies produced by hybridomas derived from lymphocytes of multiple sclerosis patients.

The aim of this study was to characterize autoantibodies produced in vitro by peripheral blood lymphocytes (PBL) of patients affected with multiple sclerosis (MS). We studied supernatants from man-mouse hybridomas established by fusion of PBL from 6 MS patients (group I) and from 13 individuals free of any neurological pathology (group II) with the mouse myeloma cell line P3X63 Ag8-653. They were screened for human IgG or IgM production by ELISA. Autoantibody activity against lymphocytes was studied by cell-binding ELISA. Anti-tissue reactivity was assessed by indirect immunofluorescence assay (IFA) on human cerebellum and peripheral nerve as well as on a panel of 8 non-nervous tissues. Additional ELISA tests were performed on 4 purified cellular antigens. Among 522 supernatants in group I, 13.7% contained Ig, mainly IgM, as compared to 25% among 1212 supernatants in group II; 8.3% in group I and 6.7% in group II contained anti-tissue autoantibodies. Antibodies against purified cellular antigens were found in 6% of the supernatants in group II versus 7% in group II. One human monoclonal anti-astrocyte antibody from group I was further studied. This IgM lambda (SAN-7) was particularly polyreactive and recognized glial fibrillar acid protein and other intermediate filaments, as well as tubulin and myosin. Moreover, cross-reactivity was observed with a hapten (TNP-BSA).

Antibodies, Monoclonal↗
PubMed1989

[Antibodies directed against the cytoplasm of granulocytes. Diagnostic value in vasculitis].

The demonstration of antibodies directed against granulocyte cytoplasm in Wegener's disease and in the microscopic forms of polyarteritis nodosa led to the proposal that these antibodies could be used as a diagnostic tool and a means to monitor the evolution of these diseases. However, the presence of these antibodies in different pathological situations and, in particular, in syndromes not related to vasculitides, poses the question as to their specificity. In addition, the observation of dissociated reactions between the methods available for the detection of these antibodies (indirect immunofluorescence, radioimmunological assay), like the existence of different morphological aspects seen in immunofluorescence, favor the hypothesis of different antigenic determinants, whose recognition could contribute to the nosology and pathophysiology of these diseases. We performed a retrospective study based on 42 positive results (paired execution of both detection techniques), in order to characterize the corresponding anatomic and clinical states. We confirmed the classical positivity in Wegener's disease and microscopic forms of polyarteritis nodosa, justified the paired running of both detection assays because of dissociated results and false positives found by immunofluorescence, corroborated the presence of antibodies in conditions apparently unrelated to vasculitides, and specified the different aspects observable by immunofluorescence, thus demonstrating the reality of different antigenic determinants.

Adolescent↗