Maria Jarzabek-Chorzelska

Clinical, serologic, and immunogenetic features in polish patients with idiopathic inflammatory myopathies

OBJECTIVE To determine the clinical, serologic, and immunogenetic correlations in patients with idiopathic inflammatory myopathies (IIM), and to evaluate the useful grouping of some diseases for practical clinical purposes. METHODS Patients with IIM were categorized according to clinical presentation as compared with autoantibody specificity. Serum samples from 84 patients were screened for myositis-specific autoantibodies (MSAs) by indirect immunofluorescence and double immunodiffusion. All sera were also studied by protein A-assisted immunoprecipitation. Genomic DNA was isolated from peripheral blood mononuclear cells, and HLA-DQA1 and DRB1 alleles were determined. The patients were seen and followed up for many years in the same center. RESULTS MSAs were present in 19% of patients. The most common MSAs were antisynthetases in 13% of patients (Jo-1 10.7%, PL-12 1.2%, and EJ 1.2%), associated with the antisynthetase syndrome. Anti-SRP was found in 1.2% of patients, associated with polymyositis, and anti-Mi-2 in 4.9%, found exclusively in patients with dermatomyositis. The most frequent MSA was PM-Scl in 23.8% of patients, associated with scleromyositis, and Ku was present in 9.6% of patients with overlap syndromes. The alleles that were found at a significantly increased frequency were HLA-DRB1*0301 (59.4%) and DQA1*0501 (71.6%), which are in linkage disequilibrium. DQA1*0501 was present in 85.7% of patients with antisynthetases, and in 100% of patients with PM-Scl and Ku. CONCLUSION The HLA-DRB1*0301; DQA1*0501 haplotype was found to be significantly increased in this population overall and in those myositis patients with antisynthetase, anti-PM-Scl, and anti-Ku antibodies. The results of this study confirm that IIM are heterogeneous syndromes, but can be divided into more useful groups on the basis of clinical, serologic, and immunogenetic features.

Scl 70 antibody—a specific marker of systemic sclerosis

Scl 70 antibodies were tested for in 107 patients with systemic sclerosis: 68 with acrosclerosis and 39 with diffuse scleroderma. Anticentromere antibodies (ACA) and other antinuclear antibodies (ANA) were tested for by indirect immunofiuorescence on HEp‐2 cells. Positive results for Scl 70 antibodies were obtained in 77percnt; of cases of diffuse scleroderma and 44percnt; of acrosclerosis. ACA and Scl 70 antibodies were found to be mutually exclusive. If acrosclerosis cases positive for anticentromere antibodies are excluded, the percentage of acrosclerosis cases positive for Scl 70 was 63percnt;. ACA were found to be a marker of a benign, abortive subset of acrosclerosis with almost no cutaneous involvement (CREST), whereas Scl 70 did not discriminate between acrosclerosis and diffuse scleroderma. On HEp‐2 cells Scl 70 positive sera gave a characteristic, fine speckled, almost homogeneous nuclear staining pattern.

Immunopathology of psoriasis.

SummaryImmunofluorescence (IF) studies by the direct and indirect methods demonstrate immunoglobulins and complement bound in vivo in psoriatic scales. The IF pattern is comparable to that of stratum corneum antibodies (SCAb) bound in vitro on specific substrate, as visualized by the indirect IF method. Formation of immune complexes can be responsible for the “squirting papilla” phenomenon, and conversion of the stratum corneum — which is normally an inaccessible antigen — into its reactive form seems to be brought about by proteases of polymorphonuclear leukocytes. Stimulation of protease production by polymorphonuclears appears to be an important factor in the pathogenesis of psoriasis. The stratum corneum of the epidermis is probably the target, and becomes an antigen for SCAb present in the circulation.ZusammenfassungUntersuchungen der psoriatischen Hautveränderungen mittels der direkten und indirekten Immunofluorescenzmethode zeigen in der Hornschicht Immunoglobulin- und Komplementablagerungen auf. Das IF-Muster ist dasselbe wie bei der Bindung der im normalen Serum auftretenden anti-Stratum corneum-Antikörper an dem spezifischen Substrat, d.h. normaler Hornschicht. Die Bildung von Immunkomplexen zusammengesetzt von anti-Stratum corneum-Antikörpern scheint das Phänomen der «Squirting papilla» zu verursachen, wobei das normalerweise nicht zugängliche Stratum corneum unter der Einwirkung von Traumen oder Leukocyten-Proteinasen antigenisch wird. Die Proteinase-Produktion durch angeregte polymorphonukleare Leukocyten ist vermutlich ein wichtiger pathogenetischer Faktor in Psoriasis, wobei das Stratum corneum das Target ihrer Einwirkung ist und reaktiv (antigenisch) wird, was die in vivo-Fixation der Stratum corneum-Antikörper ermöglicht.

Anticentromere antibody: an immunological marker of a subset of systemic sclerosis

Our clinical and immunological studies of 114 cases of systemic sclerosis, 54 of Raynauds disease and 46 of other connective tissue diseases, centered on the diagnostic and prognostic significance of anticentromere antibodies (ACA). The ACA occurred in 21 of 84 patients with acrosclerosis, in four of 54 patients with Raynauds disease but in none of 30 patients with diffuse scleroderma or transitional form, acrosclerosis‐diffuse scleroderma, or 46 cases of other connective tissue diseases. The ACA‐positive patients had no contracture or immobilization of the fingers, the indurations and/or indurative oedema were confined to fingers and usually no other types of ANA were detected. However, systemic involvement and the course of the disease were comparable in ACA‐negative and ACA‐positive acrosclerosis patients.

Autoantibodies to nucleolar antigens in systemic scleroderma: clinical correlations.

Indirect immunofluorescence (IIF) and double immunodiffusion (DID) were performed on the sera of 64 patients who had a nucleolar immunofluorescence pattern on HEp‐2 cells. Forty‐nine of the sera were from 296 patients with systemic scleroderma (SSc) and 15 sera were from 214 patients with systemic lupus erythematosus (SLE). A homogeneous nucleolar staining pattern was found in 45 of the 64 sera (70.3%), a clumpy fluorescence associated with fibrillarin antibody in 14 (21.8%) and a speckled pattern was found in five of the sera (7.8%).

Are ACA and Scl 70 antibodies mutually exclusive

Serological studies using indirect immunofluorescence, double immunodiffusion and immunoblot with recombinant Topo I and kinetochore antigens were performed in 180 patients with systemic scleroderma. In the sera of 10 patients, we found coexisting ACA and Scl 70 antibodies, and this was confirmed by all three methods. The relationship between the coexistence of these antibodies and the clinical features of the disease is not clear, although in all these cases there was pronounced vascular involvement.

The red face: Lupus erythematosus

Abstract Lupus erythematosus (LE), localized usually on the face, might be difficult to differentiate in early stages from other inflammatory dermatoses presenting as red face. The red facial lesions may be a symptom of cutaneous or systemic disease, displaying diversity of clinical features characteristic of subtypes of LE, which are discussed separately.

Immunopathologic Findings in Systemic Sclerosis Patients

ABSTRACT Direct immunofluorescence (DIF) of the skin biopsy specimens was performed in 62 patients with systemic scleroderma: 26 cases of acrosclerosis (group 1), 26 cases of diffuse scleroderma (group 2) and ten cases of transitional form acrosclerosis‐diffuse scleroderma (group 3). If epidermal nuclear fluorescence and lupus band test (LBT) were considered, the results were positive in 15.3% in group 1, 42.3% in group 2, and 10% in group 3. LBT was positive in 13.5% of the cases in groups 1 and 2 and negative in group 3. The immunoglobulin deposits at the dermoepidermal consisted mainly of IgM or a combination of IgG and IgM. There was no correlation between the LBT and antinuclear antibodies as detected by indirect immunofluorescence (IIF) or double immunodiffusion (DID).

Immunologic Markers of Systemic Scleroderma in Children

Abstract: This study was performed on seven children with systemic scleroderma, three with the diffuse and four with the limited type. All three patients with diffuse scleroderma had high titers of clumpy pattern antinucleolar antibody on HEp‐2 cells. The course of the disease was severe, and two children died. Four children with limited scleroderma had mild disease, and Scl‐70 antibody, an immunologic marker that in adults is associated mostly with diffuse scleroderma. In one child Scl‐70 antibody and anticentromere antibody coexisted, although previously the two were believed to be mutually exclusive. This study shows that limited scleroderma of childhood with slight cutaneous involvement may be associated with the Scl‐70 marker. The findings in 10 adults in whom Raynauds phenomenon developed in childhood and indurations appeared some years later, point to the sinificance of careful observation of these children, with repeated testing for immunologic markers of SSc. An important new finding is the association of different types of systemic sclerodermas with specific immunologic markers.

IMMUNOLOGIC PHENOMENA IN HERPES GESTATIONIS THEIR PATHOGENIC AND DIAGNOSTIC SIGNIFICANCE

Immunopathologic studies performed in six cases of herpes gestationis revealed a highly characteristic pattern, notably 1) BMZ deposits of complement component C3 predominates, 2) Most biopsy specimens also contain C4 and C5, 3) Deposits of C4, C5, properdin and IgG were variable in different specimens of given patients. About half of the specimens examined contained properdin and about one fourth stained for IgG, 4) Findings of IgM, IgA, IgD and IgE were consistently negative, 4) Serum findings of BMZ antibodies in given cases were variable. In two of eight cases circulating BMZ antibodies were detected in one of the samples examined. Based on these findings it seems that HG is related to BP.