Biomedical subjects

M N Manoussakis

Publications and source records attributed to M N Manoussakis.

At least 37 records · Page 2Linked to original sources

PubMed1995

Detection of human-specific anti-la(SSB) antibodies in patients with rheumatoid arthritis.

Sera from anti-Ro(SSA) positive and negative patients with rheumatoid arthritis (RA) were compared with those from patients with primary Sjogren's syndrome (pSS) and systemic lupus erythematosus (SLE) with regard to anti-La(SSB) antibodies. Several assays for anti-La(SSB) (RNA precipitation, counterimmunoelectrophoresis, and immunoblotting) demonstrated the presence of such antibodies in selected anti-Ro(SSA) positive (10/19 in RA and 18/37 in pSS and SLE) but not in anti-Ro(SSA) negative sera. In agreement with previous reports, anti-La(SSB) antibodies from pSS and SLE patients uniformly reacted with various cellular extracts used as sources of La(SSB) antigen, including extracts from human cultured cells (HeLa), calf thymus and rabbit thymus. In contrast, while all 10 anti-La(SSB) sera from RA patients reacted with the human HeLa cell extracts, only three of them also reacted with calf and rabbit thymus extracts. These results were further supported by the analysis of a cohort of 70 consecutively selected sera (displaying monospecific anti-Ro(SSA) reactivity against calf thymus extract) from patients with various rheumatic disorders, where human-specific anti-La(SSB) were detected in two out of the five of RA patients studied.

Animals↗

PubMed1994

Orthodeoxia in amiodarone-induced acute reversible pulmonary damage.

A case of acute reversible pulmonary damage from amiodarone is described. Pulmonary infiltrates had a basal predominance. The histopathologic picture was that of acute alveolitis. Orthodeoxia was evident on blood gas analysis; the PaO2 was 73 mm Hg on recumbency, and the PaO2 was 57 mm Hg in the upright position. Partial arterial resaturation was evident on exercise (PaO2, 64 mm Hg).

Amiodarone↗

PubMed1993

Detection of anti-Ro(SSA) antibodies in autoimmune diseases: comparison of five methods.

Counterimmunoelectrophoresis (CIE), RNA precipitation, ELISA and immunoblotting against cytoplasmic HeLa cell extract (IB-HeLa) and erythrocyte extract (IB-RBC) were applied to detect anti-Ro(SSA) antibodies in 93 sera selected from patients with various autoimmune diseases [47 were anti-Ro(SSA) positive by CIE]. The RNA precipitation assay, which demonstrated the highest sensitivity was selected as the reference method. CIE was found to be reliable with a specificity of 100% and a sensitivity of 89%. ELISA showed a comparable specificity (95%) but somewhat lower sensitivity (72%). Antibodies to 52 or 60 kDa Ro(SSA) proteins by IB-HeLa demonstrated a high specificity (95 and 97% respectively) but a low overall sensitivity (36 and 17% respectively). Anti-Ro(SSA) antibodies to 52, 54 and 60 kDa erythrocyte proteins by IB-RBC, had a variable overall specificity (95, 97 and 57%) and sensitivity (51, 13 and 34%). The anti-52 kDa antibodies detected by IB-HeLa correlated to those found by IB-RBC (P < 0.001) and occurred predominantly in primary Sjögren's syndrome (P < 0.001, sensitivity: 71 and 77%) as well as in sera with anti-Ro(SSA) and anti-La(SSB) antibodies (P < 0.001). These findings confirm that RNA precipitation assay has the highest sensitivity and specificity for anti-Ro(SSA) antibody detection. However, until a more sensitive ELISA is available, CIE because of its reliability appears to be the method of choice. Finally IB-RBC was found to be more sensitive than IB-HeLa for the detection of anti-Ro52 kDa antibodies.

Adult↗

PubMed1993

Immunologic and viral markers in the circulation of anti-HIV negative heroin addicts.

To assess the degree of immune system activation associated with addiction or hepatotropic viruses infection, we examined 60 HIV-negative heroin addicts for the presence of hepatitis B virus (HBV) infection markers, hepatitis C virus antibodies (anti-HCV), various auto-antibodies, and serum levels of soluble interleukin-2 receptors (sIL-2R). In addition, 28 anti-HCV positive patients comprising the disease control group, were also examined. Our results demonstrated a high prevalence of anti-HCV antibodies (61.7% and 90% with 1st and 2nd generation ELISA, respectively). Eighty-seven percent (87%) of the addicts positive for anti-HCV by the latter and 92.8% of the disease control patients, were also positive with 2nd generation recombinant immunoblot assay (RIBA-II). In 88.9% of anti-HCV positive addicts, antibody to C22-3 was the predominant (anti-C33c in 81.5%). Antibodies to C33c and C22-3 polypeptides were also more frequent in disease control group (92.8% and 85.7%, respectively). Anti-HCV antibodies were associated with increased transaminases (ALT or AST, P < 0.05), as well as with longer duration of addiction (P < 0.005). HBV infection markers (HBsAg, anti-HBc only and anti-HBs) were also present in the addicts (5%, 28.3% and 26.7%, respectively). Rheumatoid factors (RF) were detected in 36.7%, antinuclear antibodies (ANA) in 11.7%, antibodies (IgG and/or IgM) against cardiolipin (anti-CL) and double stranded DNA (anti-ds DNA) in 20% and 50%, respectively. RF, ANA, anti-CL and anti-dsDNA antibodies were also detected in the disease control group (32.1%, 89.3%, 28.5% and 28.5% respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Soluble interleukin-2 receptors, antineutrophil cytoplasmic antibodies, and other autoantibodies in patients with ulcerative colitis.

Ulcerative colitis (UC) is an inflammatory bowel disease of unknown aetiology. In this study, serum samples from 80 patients with UC were studied for the presence of various autoantibodies and soluble interleukin-2 receptor molecules (sIL-2Rs) in an attempt to determine the degree of activation of the immune system in this disease process. Autoantibodies detected included rheumatoid factors (in 5% of patients), antinuclear antibodies (in 51.3%), anti-Ro(SSA) (in 1.3%), anticardiolipin antibodies (IgG and/or IgM classes in 26.3%), anti-double stranded DNA (IgG or IgM classes in 45%), and antineutrophil cytoplasmic antibodies (ANCAs, in 30%). The ANCAs had a perinuclear pattern (p-ANCA) in 95.8%, without anti-myeloperoxidase activity, at least in an enzyme linked immunosorbent assay (ELISA) system. Raised concentrations of sIL-2R were found in 32.5% of patients (26/80, 18 with active and eight with inactive UC). The mean (SD) sIL-2R concentrations were significantly higher in patients with active UC (595 (219) u/ml v 406 (162) u/ml, p = 0.0001) and in patients with ANCAs (584 (177) u/ml in ANCA positive v 447 (212) u/ml in ANCA negative patients, p < 0.01). The sIL-2R concentrations were correlated with increased serum concentrations of C3c (r = 0.23, p < 0.05) or C4 (r = 0.4, p < 0.001) components of the complement system and erythrocyte sedimentation rate (ESR, r = 0.44, p = 0.0001). Platelets, ESR, and C3c were not associated with disease activity (p = 0.06, 0.33 and 0.86) whereas mean (SD) serum concentrations of C4 were higher in active disease (37.4 (11.9) mg/dl v 32.3 (10.3) mg/dl, p < 0.05). The sIL-2Rs had 53% sensitivity and 82.6% specificity for disease activity whereas platelet counts had 53% sensitivity and 58.7% specificity. To conclude, UC is accompanied by an autoimmune response that results in the production of several autoantibodies and cellular immune activation, as shown by the high sIL-2R concentration, is also present. The identification of the target antigen(s) of p-ANCA would possibly act as an indicator of disease activity if this distinct subset of ANCAs can be attributed to the pathogenesis of UC. The sIL-2R concentrations seem to be a useful laboratory marker for assessing activity of the disease.

Adolescent↗

PubMed1992

Serum-soluble interleukin-2 receptors in B-cell lymphoproliferative malignancies.

The levels of soluble interleukin-2 receptors (sIL-2R) were determined in the serum of 53 patients with B-cell lymphoproliferative malignancies, including 31 patients with non-Hodgkin lymphomas (NHL), 16 with chronic lymphocytic leukemia (CLL), and 6 with multiple myeloma. In addition, serum samples from 40 patients with various solid tumors as well as from 53 healthy individuals were used as controls. It was found that the mean serum levels of sIL-2R were significantly increased (P less than 0.001) in NHL (mean +/- standard error of the mean 2,327 +/- 320 units/ml) and CLL patients (2517 +/- 451 units/ml) as compared to normal controls (207 +/- 17 units/ml). No such difference was observed when the serum sIL-2R levels of patients with multiple myeloma or solid tumors were analyzed. Serum sIL-2R levels were closely related to the clinical stage, the presence of B-symptoms, and the disease activity of patients with NHL and CLL. In fact, response to chemotherapy was followed by marked decrease or normalization of sIL-2R levels, while in a number of patients sIL-2R values were even able to predict disease relapse. Finally, no association with histologic grade in NHL patients, could be demonstrated. We conclude that serum sIL-2R (1) are increased only in B-NHL and B-CLL but not in myeloma patients, (2) are related to the tumor burden, and (3) can serve as a valuable tumor marker for the monitoring of patients treatment.

Female↗

PubMed1992

Imaging of thoracic Wegener's granulomatosis: the computed tomographic appearance.

PURPOSE: Computed tomography (CT) can play a major role in the examination of patients with diffuse infiltrative disorders of the lung. CT patterns of thoracic Wegener's granulomatosis were retrospectively evaluated in this study. The CT appearance was compared with imaging obtained by conventional plain roentgenograms. PATIENTS AND METHODS: Fourteen patients with Wegener's granulomatosis seen during the last 5 years are described. Conventional chest roentgenograms and CT scans from these patients are reviewed. RESULTS: The most frequent manifestation found in the lungs of patients with Wegener's granulomatosis was that of rounded opacities with or without cavitation. This was observed in 7 of 14 patients. Relatively unexpected was the frequent occurrence of bronchovascular bundle cuffing with a quite constant and characteristic bronchocentric distribution. This finding was observed in 5 of 14 patients. Vasculitis sign was demonstrated in 2 of 14 patients. Widespread acinar infiltrates, usually confluent, were common and were seen in 5 of 14 of our patients; in 2 of the patients, these infiltrates were due to diffuse pulmonary hemorrhage. Tracheal stenosis was the cause of sudden acute respiratory failure that was observed in one patient. Pleural disease was present in 3 of 14 patients. Hilar and mediastinal lymphadenopathy was observed in one patient. An interstitial pattern was observed in 3 of 14 patients. CONCLUSIONS: We conclude that an extremely wide spectrum of radiologic findings may be observed in this disease. In 14 patients we found 11 different roentgenographic manifestations; moreover, in 8 patients it was possible to describe more than 1 radiologic manifestation at the same time or during the course of the disease. This observation is not surprising, if we consider the wide variability and broad spectrum of pathologic features in pulmonary Wegener's granulomatosis. Because conventional roentgenograms failed in a great number of cases to visualize the exact pattern and the extent of thoracic involvement, we believe that CT is particularly helpful for the assessment of pulmonary involvement in Wegener's granulomatosis.

Adolescent↗

PubMed1992

Patients with anticardiolipin antibodies with and without antiphospholipid syndrome: their clinical features and beta 2-glycoprotein-I plasma levels.

The clinical and serological features of 38 aCL-positive patients were compared to those of 45 aCL-negative patients. A significantly higher incidence of thrombophlebitis and livedo reticularis was found in aCL-positive patients. There were 13 aCL positive patients with thrombophlebitis and/or arterial thromboses and these 13 patients were designated as having the antiphospholipid syndrome (APS) while the remaining 70 patients were diagnosed as having Systemic Lupus Erythematosus (SLE). APS patients also had a high incidence of arterial occlusions, recurrent abortions and strokes compared to SLE patients. Patients with high levels of IgG-aCL were more likely to have APS, while patients with low levels of IgG-aCL or IgM-aCL only were more likely to have SLE without the clinical features of APS. Since aCL antibodies have recently been shown to interact with a phospholipid-binding plasma protein beta 2-glycoprotein-I (beta 2-GPI), we measured the beta 2-GPI levels in these patients and found that beta 2-GPI levels are significantly higher in APS compared to SLE patients negative for aCL antibodies. Since beta 2-GPI is known to exert multiple effects on coagulation processes the interaction of aCL antibodies with this glycoprotein may play a pathogenic role in APS.

Antiphospholipid Syndrome↗

PubMed1992

Impaired urinary excretion of soluble IL-2 receptors in patients with systemic lupus erythematosus and rheumatoid arthritis.

Several previous studies have demonstrated increased in vivo release of soluble interleukin-2 receptors (sIL-2R) in patients with disorders associated with cellular activation. In this study attempting to understand better the role of sIL-2R released in vivo, we investigated the sIL-2R levels in paired serum and urine samples from 25 patients with systemic lupus erythematosus (SLE), 41 patients with rheumatoid arthritis (RA) and 20 healthy subjects. Using an ELISA for sIL-2R, we detected significantly increased urinary sIL-2R levels in normal individuals (868 +/- 114 units/ml) compared to the corresponding serum samples (209 +/- 25, P < 0.001, mean urine/serum sIL-2R ratio: 4.5 +/- 0.6), which suggests that the clearance of sIL-2R from circulation is largely kidney-dependent. The patients with SLE and RA exhibited significantly increased serum sIL-2R levels compared to normals (682 +/- 115 and 734 +/- 101 units/ml, respectively, P < 0.001) and these levels correlated with disease activity. However, urinary excretion of sIL-2R in these patients (SLE: 620 +/- 154 units/ml; RA: 1084 +/- 148 units/ml) was found to be significantly decreased (mean urine/serum sIL-2R ratio in SLE: 0.9 +/- 0.2; in RA: 1.9 +/- 0.2; P < 0.001) compared to normals, possibly contributing to the accumulation of these soluble receptors in the serum of autoimmune patients after their release from cells. Our findings can be attributed either to the binding of the sIL-2R to serum protein(s) or to distinct structural features of serum sIL-2R in SLE and RA patients, interfering with the urinary excretion of these molecules.

Adult↗

PubMed1990

Factors related to the presence of autoantibodies in patients with chronic mental disorders.

Serum samples from 307 patients with various chronic mental disorders were examined for the presence of several autoantibodies. Autoantibodies detected included antinuclear antibodies (ANA) in 122/307 (39.7%), rheumatoid factor (RF) in 23/307 (7.5%), anticardiolipin antibodies (anti-CL) in 23/304 (7.6%, IgM in 12 patients, IgG in 13 patients). Isolated cases with IgG anti-dsDNA, anti-Ro(SSA), and anti-Ro(SSA)/anti-La(SSB) were also identified. The analysis of data revealed that the aging process in patients studied contributed significantly to the incidence of ANA (p less than 0.0001) and RF (p less than 0.01). In addition, the chronic administration of chlorpromazine (CPZ) was associated with the presence of ANA (p less than 0.03) as well as with the presence of IgM and/or IgG anti-CL antibodies (p less than 0.003). Finally, the diagnosis of schizophrenia correlated with the presence of ANA (p less than 0.001). This study represents the autoantibody profile of patients with chronic mental disorders and emphasizes the multifactorial origin of autoantibody response in psychiatric patients.

Adult↗

PubMed1990

Soluble interleukin-2 receptors and autoantibodies in the serum of healthy elderly individuals.

Recently, we reported an increased incidence of various autoantibodies in a healthy elderly population (Group A, 64 subjects). Presently we examined whether there is variability in the expression of the age-associated immunological aberrations between different geriatric populations by extending our observations in another healthy elderly population (Group B, 119 subjects). We also determined the serum levels of soluble IL-2 receptors (sIL-2R) attempting to define the activation status of the immune system during senescence. Compared to non-elderly controls, healthy elderly individuals exhibited a significantly higher incidence of autoantibodies as well as significantly higher levels of sIL-2R in serum (p less than 0.001), the latter possibly suggesting the occurrence of lymphocytic activation during the ageing process. The overall prevalence of autoantibodies was statistically associated with the presence of raised sIL-2R levels in serum (p less than 0.005). These aberrant immunological phenomena were more frequent among the elderly of group A, compared to group B (p less than 0.005). In contrast to the uniform expression of various autoantibodies previously observed in group A, the autoantibody profile of group B consisted mainly of rheumatoid factor and antibodies to single-stranded DNA. Finally, no association could be demonstrated between the presence of autoantibodies and HLA antigens in 42 elderly studied.

Aged↗

PubMed1989

Soluble interleukin 2 receptor molecules in the serum of patients with autoimmune diseases.

Lymphocytes upon activation release a soluble form of interleukin 2 receptor (IL-2R). Systemic autoimmune disorders are characterized by immune system disregulation associated with cellular activation; therefore we sought to determine the levels of soluble IL-2R molecules in the serum of patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and primary Sjogren's syndrome (1 degree SS). Utilizing an enzyme immunoassay method we found increased serum levels of soluble IL-2R in 65.4% (34/52) of RA, in 34.9% (15/43) of SLE, and in 25.0% (13/52) of 1 degree SS patients, compared to 4.2% (1/24) of healthy individuals. High serum levels of soluble IL-2R correlated with several indices of disease activity in RA and SLE patients, as well as with disease progression to extraglandular involvement and to pseudolymphoma or lymphoma in patients with 1 degree SS. By gel filtration analysis, the soluble IL-2R circulating in the serum of a RA patient corresponded to a high molecular weight molecule (greater than 90 kDa) compared to the 65-kDa soluble IL-2R molecule released by phytohemagglutinin-stimulated normal peripheral lymphocytes.

Adolescent↗

PubMed1989

Immunopathogenesis of Sjogren's syndrome: "facts and fancy".

Sjogren's syndrome (Ss) is an ideal model to study the pathogenesis of both autoimmunity and malignancy. It occurs as an organ specific autoimmune disease, alone or in association with almost every other autoimmune disorder, as a systemic disorder, and finally it can evolve to B-cell-lymphoid malignancy. The most consistent finding in the syndrome, the B-cell-hyperreactivity, follows the same steps of evolution. It starts as polyclonal, but not random, since the autoantibody profile correlates with the disease subgroups and the systemic manifestations and it seems to be controlled by the MHC gene composition. Further, in the systemic form of the disease it presents as a poly-oligo-mono-clonal process and ends up to monoclonal (IgMk) B-lymphoid malignancy. Studies on the T-immunoregulatory subsets and function can not explain this B-cell hyperreactivity. The initial trigger is unknown. Estrogens, known as immunoenhancers possibly promote the B-cell hyperreactivity and certain genes controlling HLA class-II MHC molecules may represent susceptibility factors for the development of the disease. The discovery of lymphokines and particularly the B-cell growth and differentiation factors as well as the rapid development of the retro-virology field may give answers pertinent to the pathogenesis of Ss and to B-cell lymphoid malignancy.

Autoantibodies↗

PubMed1988

Outcome of pregnancy in patients with autoimmune rheumatic disease before the disease onset.

The outcomes of 419 pregnancies of 154 unselected patients with various auto-immune diseases, including 390 pregnancies before the disease onset, were studied retrospectively. The patients comprised 40 with systemic lupus erythematosus (SLE), 72 with rheumatoid arthritis, 21 with primary Sjögren's syndrome (1 degree SS), 14 with progressive systemic sclerosis (PSS), and seven with mixed connective tissue disease. The histories of 267 pregnancies of 98 healthy, age matched women served as controls. Our data indicate that compared with healthy controls autoimmune patients do not experience a higher incidence of fetal loss. The incidence of fetal loss before disease onset in the various groups of autoimmune patients (as well as after disease onset in patients with SLE and RA) was not significantly different from that of controls. Spontaneous abortions in patients with 1 degree SS and PSS before disease onset occurred significantly more frequently (p less than 0.05) than in controls. Nevertheless, it should be noted that this was not the case when the incidence per woman was considered. On the other hand, patients with SLE, both before and after disease onset, experienced a higher incidence of premature deliveries (p less than 0.05). Finally, the analysis of autoantibody profiles, including antibodies to nuclear antigens, to Ro(SSA) cellular antigen, to double stranded DNA, and to cardiolipin, could not demonstrate any association of autoantibodies with any particular pregnancy outcome.

Abortion, Spontaneous↗

PubMed1988

Testing for antibodies to ENA and to dsDNA is not indicated in FANA-negative sera.

In this report, we examined whether immunofluorescent anti-nuclear antibody (FANA) test could be used as an initial screening test in identifying serum samples where subsequent testing for antibodies to extractable nuclear antigens (ENA) and to double-stranded DNA (ds-DNA), would be worthwhile. For this purpose, we retrospectively analysed the results of tests for FANA (on Hep-2 cells, positive FANA titers greater than or equal to 1:80), anti-ENA (antibodies to Ro (SSA), La(SSB), U1 nRNP and Sm, by counterimmunoelectrophoresis) and anti-dsDNA (by enzyme-immunoassay) in the sera of 488 consecutive autoimmune patients. It was found that, among the 243 serum samples with negative FANA, only two each (0.8%), had anti-ENA (weak anti-Ro (SSA) and anti-dsDNA (in low levels), respectively. In contrast, anti-ENA and anti-dsDNA were present in 28.2% and 13.5%, respectively, of the 245 FANA-positive sera (p less than 0.00001). In addition, it was found that the probability of positive tests for antibodies to ENA and to dsDNA increases proportionally to the FANA titer (p less than 0.00001). We conclude that searching for anti-ENA and anti-dsDNA in FANA-negative serum samples is generally unjustifiable.

Antibodies, Antinuclear↗

PubMed1988

[The autoantibody profile in Sjögren's syndrome].

The serological profiles of 54 patients clinically diagnosed as pSS and 92 RA patients with or without sSS were retrospectively evaluated and correlated with different SS subgroups, degree of minor salivary gland biopsy lymphocytic infiltrates, and the presence of glandular and extraglandular manifestations. Anti-Ro, anti-La and RF correlated with the development of pSS, while in RA, ANA and anti-Ro were associated with the presence of sSS, and anti-La were practically absent. In pSS patients the incidence of anti Ro and anti-La as well as the titers of ANA and RF correlated with a degree of salivary lymphocytic infiltrates (1+ to 3+). In class 4+ a substantial decrease in autoantibodies was noted. In pSS patients anti-Ro and anti-La correlated with earlier disease onset and longer disease duration, recurrent parotid gland enlargement (RPGE) and extraglandular manifestations, particularly splenomegaly and/or lymphadenopathy and vasculitis. Anti-Ro correlated with positive Schirmer's test, ANA with decreased parotid flow rate and extraglandular manifestations, whereas RF correlated with RPGE and subjective xerostomia. In RA patients autoantibodies were mainly found in the presence of xerophthalmia. ANA correlated with positive Schirmer's test, Rose-Bengal staining and subjective xerophthalmia, the latter also correlated with anti-Ro. This study reemphasized the diagnostic importance of autoantibodies for SS.

Adult↗

PubMed1987

Anticardiolipin antibodies in unselected autoimmune rheumatic disease patients.

Quantitative determination of IgG and IgM antibodies to cardiolipin (anti-CL) was performed with a newly developed sensitive and specific ELISA method. We studied a cohort of 361 unselected patients with various autoimmune rheumatic diseases (ARD), 69 patients with thromboembolic phenomena (TEP) unassociated with ARD, and 267 healthy blood donors (HBD). Anti-CL of at least one immunoglobulin class were found in 42 (11.6%) of the ARD patients, in 3 (4.3%) of the TEP patients (2 with myocardial infarction and 1 with pulmonary emboli), and in 6 (2.3%) of the HBD. In ARD patients anti-CL were more prevalent in patients with systemic lupus erythematosus (SLE) and overlap syndromes. Significant correlations included CNS involvement (particularly seizures) and features of immune hyperreactivity (splenomegaly-lymphadenopathy, ANA, and antibodies to Ro(SSA), U1-nRNP, and double-stranded DNA). No statistical correlation could be demonstrated between the presence of anti-CL and thrombotic events, hematologic disorders, or recurrent abortions in the ARD patients.

Adolescent↗

PubMed1987

Pulmonary involvement in systemic sclerosis. Association with anti-Scl 70 antibody and digital pitting.

The association of clinical and serologic features of 34 patients with systemic sclerosis was examined. Anti-Scl 70 antibody was found to identify patients with abnormal pulmonary function, particularly impaired diffusion (p less than 0.005), as well as patients with digital pitting scars (p less than 0.025). In addition, the presence of digital pitting scars correlated with impaired diffusion (p less than 0.005), suggesting that interstitial pulmonary disease in systemic sclerosis may, like digital pitting, be secondary to vascular pathology. Anticentromere antibody-positive patients were less likely to have abnormalities of pulmonary function (p less than 0.001).

Autoantibodies↗