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Biomedical subjects

A Gabrielli

Publications and source records attributed to A Gabrielli.

At least 19 recordsLinked to original sources

Juvenile rheumatoid arthritis patients manifest immune reactivity to the mycobacterial 65-kDa heat shock protein, to its 180-188 peptide, and to a partially homologous peptide of the proteoglycan link protein.

Immune reactivity to the 65-kDa mycobacterial heat shock protein (hsp65) has been associated with arthritis in rats and humans. In this report we evaluated patients with juvenile rheumatoid arthritis for such immunity. A high proportion of affected children showed both antibody and T lymphocyte responses to hsp65 and to two related peptides: the nonapeptide 180-188 sequence of hsp65 and a partially homologous peptide of the cartilage proteoglycan link protein. The titer of circulating antibodies was generally higher in patients with clinically active disease. In contrast to the juvenile rheumatoid arthritis patients, patients with adult rheumatoid arthritis tended to have lower responses of their peripheral blood T lymphocytes to the whole hsp65 molecule. Moreover, the adult rheumatoid arthritis patients did not respond to the peptides. Thus, there appear to be immunological differences between juvenile and adult forms of rheumatoid arthritis related to hsp65 reactivity.

Adolescent

Antibodies to mycobacterial 65 kDa heat shock protein in systemic sclerosis (scleroderma).

It has been reported that immunity to the 65 kDa heat shock protein of Mycobacterium tuberculosis (MT-hsp65) not only accompanies rheumatoid arthritis (RA), but may also be characteristic of chronic inflammation. We now report serum antibodies to MT-hsp65 in 47% of systemic sclerosis (SSc), 38% of primary Raynaud's phenomenon (PRP) and 5% of systemic lupus erythematosus (SLE). Antibody levels were higher in patients with active or progressive SSc and correlated with the degree of skin fibrosis. Thus, immunity to MT-hsp65 appears in SSc and is not limited to RA. However, it does show some degree of specificity beyond chronic inflammation: PRP patients have a higher reactivity than do SLE patients.

Adolescent

Oropharyngeal and esophageal function in scleroderma.

Fifty-one patients with systemic sclerosis (scleroderma) underwent videofluoroscopy during barium swallow to evaluate the incidence of oropharyngeal deglutition abnormalities and to correlate the radiologic patterns of esophageal motility abnormalities with patients' clinical features. Thirteen patients (26%) showed swallowing dysfunction, (e.g., oral leakage, retention, penetration, mild or moderate aspiration, and upper esophageal sphincter incoordination). These dysfunctions were more severe in patients with prominent esophageal dysmotility. Normal esophageal motility was not associated with swallowing alterations. Patients with an oropharyngeal disorder had a higher incidence of pulmonary disease. The clinical picture of the above-mentioned 13 patients was more severe, based on the duration of Raynaud's phenomenon and duration of skin sclerosis. Patients with primary Raynaud's phenomenon had no oral or esophageal abnormalities. The esophageal phase of swallowing was abnormal in 80% of the patients with scleroderma. Esophageal dysfunction, therefore, seems to be frequent in the early stages of the disease. However, patients with advanced or extensive disease may have normal esophageal function.

Adult

Antibodies to mouse laminin in patients with systemic sclerosis (scleroderma) recognize galactosyl (alpha 1-3)-galactose epitopes.

Employing radioimmunoinhibition assays with distinct oligosaccharides as inhibitors, this study demonstrates that the epitope recognized on mouse laminin by sera from patients with systemic sclerosis (scleroderma) is a terminal galactosyl (alpha 1-3)-galactose disaccharide. The reaction with this alpha-digalactose was further confirmed when the sera were tested in radioimmunoassay (RIA) binding assay and in ELISA with synthetic galactose alpha 1-3 galactose coupled to human serum albumin. The circulating antibody appeared restricted to the IgG class and mostly to the subclass IgG3 and IgG4. Antibodies with the same specificity can be found in patients with American cutaneous leishmaniasis and Chagas disease; however, whilst in these diseases the antibody production is triggered by antigenic determinants present on the surface of the parasites, the events eliciting their appearance in systemic sclerosis are unknown.

Disaccharides

[Correlation between the radiologic study of deglutition and the clinical picture in systemic sclerosis (scleroderma)].

Fifty-one patients with systemic sclerosis (scleroderma) were studied by means of videofluoroscopy in order to evaluate the abnormalities in the oropharyngeal and esophageal phases of deglutition and to correlate the radiological patterns with the clinical features of the disease. Thirteen patients (25.5%) exhibited swallowing disorders such as oral leakage, retention, penetration, mild or moderate aspiration and abnormal upper esophageal sphincter behavior. These dysfunctions were more evident in patients with esophageal motility abnormalities. A normal radiological pattern in the esophagus was not associated with swallowing alterations. Remarkably, patients with oral-pharyngeal disorders had a higher incidence of lung diseases. Forty-five patients (88%) exhibited disorders of the esophageal phase of deglutition, such as mild or severe motility abnormalities or hiatal hernia, gastro-esophageal reflux, reflux esophagitis, and stricture. Radiological findings in the esophagus can be abnormal in the early stages of the disease. On the other hand, the radiological pattern of esophageal motility can be occasionally negative in advanced or extensive disease. This indicates a discrepancy between clinical symptoms and radiological picture of the esophagus. The radiological examination of the oral-pharyngeal and esophageal phases of deglutition is important in patients with scleroderma in order to evaluate visceral involvement, motility disorders, and risk of aspiration. Such radiological information can be useful in preventing esophagitis and pulmonary complications.

Adult

A retrospective study of antibodies against basement membrane antigens (type IV collagen and laminin) in patients with primary and secondary Raynaud's phenomenon.

Antibodies against type IV collagen were detected in the sera of 21% of patients with primary Raynaud's phenomenon (PRP) and 68% of patients with systemic sclerosis. Sera from 25% of the PRP patients and 48% of systemic sclerosis patients displayed antibodies to laminin. Eighty percent of the patients with PRP and antibodies to basement membrane antigens developed additional serologic or clinical manifestations, whereas only 16% of patients with PRP and no anti-basement membrane antibodies developed such manifestations.

Adolescent

Assessment of disease activity in essential cryoglobulinemia by serum levels of a basement membrane antigen, laminin.

When compared with 40 normal controls, 46 patients with essential cryoglobulinemia had higher serum concentrations of a basement membrane antigen, laminin fragment P1 (LP1). Serum LP1 values were more pronounced in patients with visceral involvement, compared with those with skin vasculitis only. Asymptomatic patients or those with arthralgia usually had normal values. Increased disease activity was associated with a significant increase in LP1 (P less than 0.01). For evaluation of disease activity, determination of serum LP1 was a more sensitive measure than any complement factor assay.

Adolescent

Depression by Fc gamma receptor ligands of SRBC-induced IgM-PFC generation in human blood mononuclear cell cultures.

A tissue-culture system to stimulate human peripheral blood mononuclear cells (PBMC) has been employed in which IgM plaque-forming cell (IgM PFC) generation in response to sheep erythrocytes (SRBC) is dependent on macrophages and T suppressor and helper lymphocytes. In this system PBMC from normal subjects give IgM PFC responses ranging from 26 to 938 PFC/culture. Heat-aggregated human IgG or immune complexes present for the duration of culture induce a significant depression of PFC. Unaggregated IgG has no effect on the response or only a moderate stimulatory effect at the highest dose. The results of these experiments are compatible with previous results in a murine system, which indicated that Fc gamma receptor-positive (Fc gamma R+) cells in the suppressor subset are the target for aggregated IgG and induce depression of the PFC response. A similar mechanism may be operating in the human system described here, although the target cell has not been identified. These results may reflect a mechanism of immunomodulation dependent on interaction of Fc receptor (FcR) ligands with FcR, which may play a role in the pathogenesis of immune complex disorders.

Antibody-Producing Cells

Mononuclear cells from rheumatoid arthritis patients exhibit a depressed IgM response to sheep erythrocyte stimulation in vitro.

Human peripheral blood mononuclear cells when cultured for the short term (11 days) produce an optimal IgM plaque-forming cell (PFC) response to sheep erythrocytes, which is dependent on macrophages and T suppressor and helper lymphocytes. With this system we have investigated the PFC response of individuals with rheumatoid arthritis and compared this to the response of normal sex- and age-matched controls and of patients with osteoarthritis. The response of rheumatoid arthritis patients was significantly lower than that of subjects in the other two categories.

Animals

Levels of type IV collagen and laminin fragments in serum from patients with progressive systemic sclerosis.

Sera from patients with progressive systemic sclerosis (PSS) were studied using immuno-assays for laminin P1 fragment and the carboxyterminal NC1 domain from type IV collagen. Compared to healthy controls, patients with PSS showed elevated serum levels of both fragments derived from basement membrane proteins. However, there was no difference when patients with and without Raynaud's phenomenon were compared and no correlation could be established with the activity of the disease or clinically defined types of scleroderma. Our data indicate that the metabolism of basement membrane proteins is involved in the course of scleroderma; however, it remains questionable whether these assays could become useful as diagnostic or prognostic tools.

Collagen

Evidence of immune deposits and of basement membrane alterations in dermal vessels of normal skin of patients with essential mixed cryoglobulinemia.

To gain insight into the pathogenic mechanisms of immune complex-mediated vasculitis, clinically normal skin specimens from the forearms of 12 patients with essential mixed cryoglobulinemia were investigated by light microscopy, immunofluorescence microscopy, and electron microscopy. Basement membrane alterations were documented in 9 patients. Eleven patients had deposits in vessel walls, but only in 1 was there evidence of inflammation. The same immunoglobulins of the cryoproteins could be demonstrated in the tissue deposits by immunofluorescence analysis and by immunoelectron microscopy. These findings suggest that, in essential mixed cryoglobulinemia, immune reactants in dermal vessels of normal skin are more common than is evidenced by clinical examination. Moreover, it seems that cryoglobulins, as such, are not sufficient to trigger an inflammatory process: Additional local or plasma factors are required. Deposits were absent in 7 patients with cryoglobulinemia that was associated with a primary disorder. This could be ascribed to the lower cryocrit levels documented in this group of patients, or to the shorter duration of their disease.

Adult

HLA class I- like antigen expression on human leukemic cells.

The expression of HLA class I- like molecules was analyzed on human acute and chronic leukemic cells. The presence on leukemic cells of class I- like molecules, absent on the patient's normal lymphocytes, was examined by complement- dependent lymphocytotoxicity using platelet absorbed alloantisera that recognize HLA-linked, 45-12 kd, beta-2-microglobulin associated molecules, selectively expressed on PHA-activated cells. A positive reactivity of the anti- class I- like alloantisera was found in 50% of the acute leukemias (cALL, T-ALL and AML), independently of the lineage of differentiation, while chronic lymphocytic leukemias (B-CLL) were constantly negative. It is suggested that beta-2-microglobulin associated HLA molecules may represent markers of leukemic blast activation and/or maturation state.

Adult