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Biomedical subjects

I Wichmann

Publications and source records attributed to I Wichmann.

At least 37 records · Page 2Linked to original sources
PubMed1997

Cytoplasmic detection of a novel protein containing a nuclear localization sequence by human autoantibodies.

A great diversity of antibodies directed to cell proteins has been described in sera of patients with autoimmune diseases. Most of these sera recognize nuclear components, but some others are directed against cytoplasmic autoantigens. Some of the antibodies directed to cytoplasmic autoantigens are well characterized, such as anti-mitochrondial, anti-ribosomal, anti-microsomal and anti-Golgi complex autoantibodies, but the target of many others remains unknown. In the last 5 years we have selected 32 sera with a characteristic speckled cytoplasmic pattern in indirect immunofluorescence (IIF) assay among a total of more than 31,000 sera from patients with any kind of autoimmune manifestation who attend our Connective Tissue Disease Clinic. Using a human cDNA expression library, we have identified a new autoantibody specificity named RCD-8 in five of these sera, directed to one cytoplasmic autoantigen. Affinity-purified antibodies eluted from a positive clone reproduced the same IIF cytoplasmic staining pattern as native serum and reacted with one single band of 160 kD on an immunoblot of HeLa cell extract. The sequence was found homologous to an autoantigen recently reported named Ge-1, and contains a nuclear localization sequence (NLS), an active protein domain made by a contiguous stretch of amino acids which allows the selective entry of the protein into the nucleus. The five patients whose sera exhibited this new autoantibody specificity displayed different autoimmune pathological profiles.

Amino Acid Sequence↗
PubMed1997

Presence of glomerular basement membrane (GBM) antibodies in HIV- patients with Pneumocystis carinii pneumonia.

Following the unexpected finding of antibodies to GBM in a patient with Pneumocystis carinii pneumonia in the absence of kidney abnormalities, the presence of anti-GBM antibodies was analysed in 14 patients with pulmonary P. carinii infection who did not have clinical evidence of autoimmune glomerulonephritis. Patients were divided into three groups: HIV- with P. carinii pneumonia (n = 4), HIV+ with P. carinii pneumonia (n = 5) and HIV- carriers of P. carinii without pneumonia (n = 5). As control groups, HIV- patients with community-acquired non-P. carinii pneumonia (n = 6) and healthy individuals (n = 16) were included. Anti-GBM antibodies, studied with a quantitative enzyme immunoassay (EIA) for anti-alpha3 chain of collagen IV antibodies, were detected in three out of the four HIV-patients with P. carinii pneumonia, but not in any individuals of the other categories. These results suggest that P. carinii alveolar injury or the host response to the organism could affect the basal membrane Goodpasture antigen or a similar antigen, and induces anti-GBM antibody production in HIV- patients, and support the hypothesis that, at least in some cases, Goodpasture's syndrome could be triggered by an alveolar lesion induced by a P. carinii pneumonia.

Adult↗
PubMed1996

Presence of antibodies to replication protein A in some patients with systemic lupus erythematosus (SLE).

Presence of antibodies directed against replication protein A (RPA), a DNA binding protein complex composed of three subunits (RPA-70, RPA-32 and RPA-14) was investigated among patients with SLE and other autoimmune diseases using immunoblot analysis to RPA-70 and RPA-32 recombinant proteins. Anti-RPA antibodies were found in two out of 108 sera from SLE patients, one of them showing reactivity against RPA-32 and RPA-70 and the other reacting only against RPA-32. Sera from 108 patients with other autoimmune disorders as well as from 42 healthy control individuals were negative. Thus, the frequency of these antibodies in SLE is estimated to be 2-3%. The study demonstrates that RPA is one target more of the wide array of autoantigens that elicit an immune response in SLE. The presence of anti-RPA autoantibodies seems to be circumscribed to a small number of patients with SLE.

Adult↗
PubMed1996

Antimyeloperoxidase antibodies in individuals with occupational exposure to silica.

OBJECTIVE: To determine the prevalence of autoantibodies to myeloperoxidase (MPO) in a series of patients exposed to silica. METHODS: The study included 52 patients with occupational exposure to silica (mean exposure time seven years) and a control group comprising seven patients with progressive systemic sclerosis (PSS), six patients with systemic lupus erythematosus (SLE), and 15 healthy individuals. Antibodies to MPO were detected using commercial enzyme linked immunosorbent assay (ELISA) plates coated with MPO. Indirect immunoflurescence studies for antineutrophil cytoplasmic antibodies were performed using ethanol and formol fixed neutrophils. Clinical and biological data of individuals exposed to silica were recorded (published previously). RESULTS: Antibodies to MPO were detected in 14 individuals exposed to silica (27%). There was a statistically significant difference in anti-MPO ELISA units between the healthy subjects and patients (SLE, PSS, silica exposed individuals) (p < 0.01), but no difference between the different disease groups. CONCLUSIONS: Individuals chronically exposed to silica, whether or not they have a connective tissue disease, have levels of antibodies to MPO (as detected by ELISA) that are greater than those found in the normal population, but similar to those in patients with systemic diseases not induced by silica (SLE/PSS).

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1996

[The use of interferon alfa-2r in the treatment of autoimmune uveitis (primary or associated with Behçet's disease)].

BACKGROUND: The improvement in ocular inflammation in patients with cyclosporine A resistant Behçet disease (CyA) during therapy of severe aphthosis with recombinant interferon-alpha 2b (IFN alpha) prompted its evaluation for treatment of refractory autoimmune uveitis. METHOD: IFN alpha was used in 18 patients with posterior uveitis, nine with Behçet disease and nine with primary uveitis (mean evolution time 3.8 years) previously treated with corticosteroids (18), CyA (16) and azathioprine (1). The dose was 5 MU/day (4 weeks) and then twice weekly (12 weeks) maintaining the previous therapy. Evaluations were made at the start of the study, two weeks and two months and a cross-sectional study in February 1995. RESULTS: At the early phase both vitreal cellularity (p = 0.01) and macular edema (p = 0.003) improved; at the late phase improvements were noted in vitreal cellularity (p < 0.0001), macular (p < 0.0001) and papillar edema (p = 0.04) and visual acuity (p = 0.006). In February 1995 (mean evolution time 30 months), ten patients (56%) remain without treatment with inactive disease, six (33%) with CyA and two (11%) with CyA and IFN alpha. Improvements in vitreal cellularity (p = 0.0001), macular edema (p = 0.0001) and visual acuity (p = 0.013) were still present although macular ischemia was more severe than at the beginning (p = 0.035). The most important adverse reactions (late reactions) included depression (three cases) and thyroid changes (two cases). CONCLUSIONS: IFN alpha is an important therapeutic alternative for posterior uveitis refractory to corticosteroid therapy (included CyA).

Adolescent↗
PubMed1995

Presence of antibodies to different subunits of replication protein A in autoimmune sera.

A human cDNA expression library was used to investigate the nature of molecules recognized by serum from a patient with Sjögren syndrome that exhibits a mixed immunofluorescence pattern and reacts with multiple components on an immunoblot. The data demonstrated that this serum contains IgG antibodies specific for the 70- and 32-kDa subunits of replication protein A (RPA; RPA-70 and RPA-32, respectively), a highly conserved multisubunit DNA binding protein. Affinity purification of serum autoantibodies demonstrated a complete lack of cross-reactivity between RPA-70 and RPA-32, suggesting a direct participation of the native protein complex in the autoimmune response in this patient. Purified anti-RPA-70 and anti-RPA-32 antibodies labeled nuclear and cytoplasmic components in an immunofluorescence assay, suggesting that RPA is present in both cellular compartments. Additional sera from 55 patients with different autoimmune conditions were screened against purified RPA-70 and RPA-32 recombinant proteins. One of these 55 sera was positive and reacted with only RPA-32. Twenty sera from healthy control individuals did not react with RPA. These results show that RPA is a target for autoantibodies in human autoimmune diseases, although its precise frequency, occurrence in other autoimmune diseases, and pathological significance remain to be fully elucidated.

Antibody Specificity↗
PubMed1995

[The efficacy of cyclosporin in the treatment of myositis].

Cyclosporin A (CyA) was used in 15 patients with corticosteroid-resistant myositis (11) and as a first-line drug (4). The criterion for improvement was recovery of strength. Additionally, changes in muscle enzyme values were evaluated. One patient left therapy because of gastric intolerance. Another patient, with severe pulmonary fibrosis, died 6 days after initiating therapy. In the other patients a favorable response was observed at approximately six weeks (range 3 weeks-3 months). Significant decreases in muscle enzyme values were observed. CyA was useful for treatment of corticosteroid-resistant patients. While it was efficient as a first line drug, the present report does not allow a comparative evaluation with corticosteroid therapy.

Adult↗
PubMed1993

Multiple clinical and biological autoimmune manifestations in 50 workers after occupational exposure to silica.

OBJECTIVES: A self referred group of four workers from a factory producing scouring powder with a high silica content showed a surprisingly high number of features compatible with a connective tissue disease. Further subjects working at the same factory were subsequently studied to evaluate the relation between this exposure and the development of autoimmune processes. METHODS: A total of 50 subjects (44 women, six men; mean (SD) age 43.7 (5.5) years; mean duration of employment 6.1 years) underwent a prospective study including clinical history and physical examination, an immunobiological study, HLA typing, radiological and functional oesophageal and respiratory examination, ophthalmological examination, and isotopic testing of salivary glands. RESULTS: Symptoms of a systemic illness were present in 32 (64%) subjects: six with Sjögren's syndrome; five with the criteria for systemic sclerosis; three with systemic lupus erythematosus (SLE); five with an 'overlap syndrome'; and 13 with undifferentiated findings not meeting the criteria for a defined disease. Antinuclear antibodies were present in 36 (72%) subjects; four had antibodies to native DNA, including two subjects with SLE, one with systemic sclerosis associated with secondary Sjögren's syndrome, and one with overlap syndrome. Anticentromere antibodies were not detected. The frequency of HLA-DR3 was increased in the clinically affected subjects, but did not reach statistical significance. CONCLUSIONS: This descriptive study emphasises the high probability of workers occupationally exposed to silica developing a multiple spectrum of clinical and serological autoimmune manifestations.

Adult↗
PubMed1992

A human monoclonal autoantibody to a nucleolar structure.

Peripheral blood lymphocytes from a scleroderma patient (CDC) were isolated, transformed with Epstein-Barr virus and fused to the heteromyeloma SHM-D33. Supernatants from cultures were screened for autoantibody production against nucleoprotamine by ELISA. Positive wells were cloned by limiting dilution. After cloning, supernatants from two wells were positive for the nucleoprotamine assay. One named CDC-1 has been studied in our laboratory. CDC-1 recognized a nucleolar antigen by indirect immunofluorescence. By using an ELISA with purified recombinant antigens, CDC-1 reacted against Ro/SS-A, U1 (RNP) and Sm. By immunoblotting using a lysate of MOLT-4 cell line, CDC-1 was able to react against a structure of 60 kD. When the antigen recognized by CDC-1 was purified, SDS-PAGE under reducing conditions with purified antigen and subsequent silver staining of the gel allowed us to detect three bands at 60, 55 and 39 kD, respectively. A screening by ELISA with previously characterized antisera against our purified antigen demonstrated reactivity of the CDC-1 antigen with those antisera able to recognize Ro/SS-A.

Antibodies, Antinuclear↗
PubMed1989

[Serum and immunological markers of progression to acquired immunodeficiency syndrome in hemophiliacs].

In a cohort of 30 randomly selected hemophiliacs who were prospectively controlled for four years the predictive value of AIDS development was evaluated for serum markers of HIV infection and for lymphocytic subpopulations in peripheral blood. The patients were evaluated with a mean of 15.79 +/- 5.74 months, and overall antibodies, specific antibodies (anti-ENV and anti-p24), HIV antigen (Ag HIV) and lymphocyte subpopulations were determined. 50% of the hemophiliacs with positive serum Ag HIV (2/4) developed AIDS during the study, whereas this progression was not recorded in any anti-HIV positive, nonantigenic patient. The presence of Ag-HIV was detected at least two years before the diagnosis in these patients, and it was associated with the absence of anti-p24 in one or more determinations. The immune regulation parameters were not significantly different, at the beginning of the study, in the hemophiliacs who developed AIDS and in those who did not. However, the progression to AIDS was associated with a significantly smaller T4/T8 ratio at least one year before the diagnosis. Our results show that the development of AIDS in hemophiliacs is associated both with the presence of Ag-HIV in the serum and a reduction in the T4/T8 ratio, although the detection of the former appears to be earlier than that of the latter in this risk group.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Contrasting features of insulin dependent diabetes mellitus associated with neuroectodermal defects and classical insulin dependent diabetes mellitus.

The Wolfram, or DIDMOAD, syndrome is a rare congenital disease that is associated with diabetes insipidus, insulin dependent diabetes mellitus of an early onset, bilateral optic atrophy and deafness. Urological disorders are usually present as well. We have studied nine patients belonging to five different families. All of the family members were HLA typed (including DR), and islet cell as well as antinuclear antibody determinations were carried out. Although individuals with insulin dependent diabetes mellitus are very prone to have either HLA-DR3 or -DR4 antigens, none of our patients had DR3 antigens and only one was DR4 positive. On the other hand, three of our patients were typed as HLA-DR2 positive. This antigen is uncommon in classical insulin dependent diabetes. In one of the families, the affected siblings did not share the same HLA haplotype. Islet cell and antinuclear antibodies were not found in any of the cases and six of the patients had a small, but significant, insulin secretory reserve. On the basis of some of the clinical features it was also possible to further distinguish between the DIDMOAD syndrome and the classical insulin dependent diabetes mellitus. The differences encountered between classical and DIDMOAD insulin dependent diabetes mellitus--the presence/absence of HLA linkage, HLA-DR2, -DR3 and -DR4 associations, islet cell or antinuclear antibodies, the tendency to ketosis and diabetic retinopathy--indicate that their etiopathogenies are triggered by distinct mechanisms.

Adolescent↗
PubMed1985

Antibodies to human T-cell leukemia virus type III in hemophiliacs from Spain.

We tested serum samples from 50 hemophiliacs from Sevilla, Spain, for antibody to HTLV-III by indirect membrane immunofluorescence (IMI) and radioimmunoprecipitation with SDS polyacrylamide gel electrophoresis (RIP-SDS/PAGE). All had received commercial clotting factors from the United States with the exception of one hemophiliac who had never been transfused. Thirty-four (68%) reacted with HTLV-III-infected cells (H9/HTLV-III) by both methods, but not with the uninfected line (H9). Of 41 hemophilia-A patients tested, 28 (68%) were positive, and of nine hemophilia-B patients, six (66%) were positive. The nontransfused hemophilia-B patient was negative for antibody to HTLV-III by both methods. One patient with clinical AIDS tested positive as did six of seven with chronic unexplained lymphadenopathy. The eight individuals with AIDS or lymphadenopathy all had hemophilia A. We conclude that exposure to HTLV-III is widespread among asymptomatic hemophiliacs in Spain.

Adolescent↗