PubMed Health⌕ Search

Biomedical subjects

H M Moutsopoulos

Publications and source records attributed to H M Moutsopoulos.

At least 73 records · Page 4Linked to original sources
PubMed2000

No evidence of epitope spreading after immunization with the major Sm epitope P-P-G-M-R-P-P anchored to sequential oligopeptide carriers (SOCs).

The sequence Pro-Pro-Gly-Meth-Arg-Pro-Pro (PPGMRPP) is the major B-cell epitope of the Sm autoantigen. The aim of the present study was to evaluate the immune response against the native forms of Sm and U1RNP and immune mediated tissue injury after immunization with the sequence PPGMRPP anchored in five copies to a new type helicoid sequential oligopeptide carrier (SOC) formed by the repetitive Lys-Aib-Gly moiety, [(PPGMRPP)(5)SOC(5)]. Rabbits (n=3) were immunized with 0.5 mg of (PPGMRPP)(5)SOC(5)in complete Freud's adjuvant and boosted at days 26, 53, 99; control rabbits were immunized with the PPGMRPP alone (n=3), phosphate buffered saline (PBS) (n=1), SOC(5)alone (n=1), a peptide at aminoacid (aa) position 158-177 of myelin basic protein (MBP aa 158-147) (n=1) and three La/SSB autoantigen B-cell epitopes (n=3). Antibodies to (PPGMRPP)(5)SOC(5)were determined by enzyme linked immunosorbent assay (ELISA); precipitating anti-Sm and anti-U1RNP antibodies were detected by RNA precipitation and western blot on HeLa total cellular and nuclear extract and 12s sucrose gradient fraction of rat liver extracts. High titres of anti-(PPGMRPP)(5)SOC(5)antibodies not recognizing the native forms of Sm or U1RNP antigens were detected in the (PPGMRPP)(5)SOC(5)immunized but not in the control animals. The sera of two (PPGMRPP)(5)SOC(5)immunized but not of the control rabbits recognized a 67 kDa protein in HeLa nuclear extract, distinct from the 70 kDa U1RNP antigen. Diffuse and segmental increase of mesangeal matrix and cells, crescent formation, segmental glomerular necrosis, rarely massive subendothelial deposits occluding the lumen and C3 complement component in the mesangeal area were seen in the kidneys of one (PPGMRPP)(5)SOC(5)immunized, but not of the remaining animals. In conclusion, the immune response induced by (PPGMRPP)(5)SOC(5)was specific for the immunizing epitope but not for the native forms of Sm and U1RNP antigens, but it was associated with immune mediated kidney injury.

Amino Acid Sequence↗
PubMed2000

Erythema nodosum: the underlying conditions.

Erythema nodosum (EN) is a cutaneous reaction consisting of inflammatory, tender nodular lesions and is associated with a wide variety of disease processes. The aim of our study was to investigate the frequency of different aetiologies of EN. One hundred and thirty-two EN patients were investigated in a prospective study during the period 1984-1990. The evaluation of all patients began with a medical and family history and completed with a thorough physical examination and detailed laboratory and immunological work-up. In addition, various diagnostic procedures were performed where and when indicated. One hundred and ten patients (83%) were women. Their mean age was 41.0+/-14.0 years, range 18-79 years. In 35% the cause of EN was not found. Sarcoidosis was revealed in 28% of the patients, infections in 17.3% and tuberculosis in 1.5%. Other aetiologic factors were Adamantiadis-Behçet's syndrome (3.8%), pregnancy (6%), oral contraceptives (3.8%) and other drugs (3.8%). The aetiology of EN was not found in 35% of the patients. Sarcoidosis and infections were frequent causes of EN, whereas autoimmune rheumatic diseases rarely cause EN.

Adolescent↗
PubMed2000

Clinical evolution, and morbidity and mortality of primary Sjögren's syndrome.

OBJECTIVES: To study the clinical and laboratory profile evolution, as well as morbidity and mortality impact, of primary Sjögren's syndrome (pSS), in a large cohort of patients followed-up longitudinally. METHODS: We studied the evolution of the clinical picture and laboratory profile of pSS, the incidence and predictors for systemic sequelae, and the impact of pSS on overall survival in a prospective cohort study of 261 patients with pSS. Analyses included calculation of incidence rates, Cox proportional hazards predictive models, and estimation of standardized mortality ratios (SMRs) compared with the general Greek population, adjusting for age and sex. RESULTS: Glandular manifestations of the syndrome were typically present at the time of diagnosis. Systemic manifestations such as arthritis, Raynaud's phenomenon, purpura, interstitial nephritis, and liver involvement, as well as the serological profile, also did not change substantially during subsequent follow-up. Incidence rates for peripheral neuropathy, glomerulonephritis, and lymphoproliferative disorders were 3.3, 6.6, and 12.2 per 1,000 person-years, respectively. Glomerulonephritis and lymphoma tended to co-exist in the same patients (relative risk, 34.0; P < .0001). The development of lymphoproliferative disorders was associated with low levels of C4 complement (relative risk, 7.5; P = .0016), the presence of mixed monoclonal cryoglobulins (relative risk, 7.9; P = .0012), and purpura (relative risk, 3.9; P = .037). Low levels of C4 was the strongest predictor for mortality after adjusting for age (relative risk, 6.5; P =.0041). Patients with pSS had an SMR of 2.07 (95% CI, 1.03 to 3.71). However, when patients with adverse predictors were excluded, the mortality rate was identical to that of the general population (SMR 1.02). CONCLUSIONS: The initial presentation of pSS determines subsequent outcome. Purpura, decreased C4 complement levels, and mixed monoclonal cryoglobulinemia are adverse prognostic factors. The overall mortality of patients with pSS compared with the general population is increased only in patients with adverse predictors.

Adolescent↗
PubMed2000

Neuroendocrine manifestations in Sjögren's syndrome.

Molecular biology has had a major impact on our concepts of the immune system and its relation to neuroendocrine axes, in particular, the adrenal, gonadal, and thyroid axes. It is now well established that not only are the biosynthetic and catabolic pathways of glucocorticoids and sex hormones (estrogen, progesterone, and testosterone) closely related but that the receptors for these hormones are part of a supergene family of receptors which include (in addition to these hormone receptors) the mineralocorticoid receptor, thyroid hormone receptor, retinoic acid receptors, and vitamin D receptors. This suggests a complex network of steroid hormones and receptors for the control and integration of a multitude of physiologic functions at a systemic level. The immune system seems to be tightly integrated into this homeostatic neuroendocrine regulatory network. The neurophysiologic and biochemical events that promote successful adaptation during stressful situations are now identified for illnesses that seem to occur as a result of or are associated with dysregulation of the stress response. One difficulty in interpreting the mechanisms of HPA axis dysfunction in autoimmune-inflammatory syndromes arises from the plasticity of the hormonal systems involved. Levels of hormones produced and receptors reset rapidly with changes in the hormonal milieu (deficiency or excess) and have likely changed during the course of the chronic immune disorder. This, in turn, is further confounded by the pleomorphic natural history of most autoimmune-inflammatory diseases such as SS. The levels of sex hormones and their receptors are tightly linked to HPA axis function. It may be that significant changes in the estrogen-to-androgen ratio or the ratio of their receptors alter the activity of steroid-sensitive cells such as the individual immune cells or epithelial cells, thus providing a means for endocrine regulation of the immune response in SS. Studies in the closely related disorder RA support this hypothesis. Taken together, adrenal and gonadal steroid hormone deficiency plus elevated PRL levels probably greatly facilitate cellular immunity in SS patients. This hypothesis in SS is supported by a growing body of data indicating that RA develops as a consequence of a deficiency in adrenal and gonadal steroid hormone production. It is noteworthy that the findings in female SS patients indicated a central deficiency in all three neuroendocrine axes: adrenal, gonadal, and thyroid. At present, it is not clear if any one system plays a primary role in the expression of the disease. Rather, it is likely that the net effect involves the synergistic and antagonistic effects of multiple hormones, making the specific effects of individual hormones difficult to discern.

Gonadal Steroid Hormones↗
PubMed2000

Dental and periodontal status of Sjögren's syndrome.

BACKGROUND: Sjögren's syndrome (SS) is one of the most common systemic autoimmune diseases in middle-aged women. The present study had the aim to examine the dental and periodontal condition in patients with SS in comparison with disease controls and to evaluate the influence of reduced salivary flow in the periodontal tissues. METHOD: We examined 24 patients with primary or secondary SS in comparison with 27 patients who had another autoimmune disease but no signs or symptoms of SS, as well as with 29 subjects who had a subjective feeling of xerostomia or xerophthalmia without exhibiting an underlying disease. The clinical evaluation included examination of the oral mucosa, determination of missing, decayed and filled teeth, fixed or removable prosthetic appliances, plaque index, gingival index, probing pocket depth, probing attachment level, oral hygiene habits and frequency of dental visits. Statistical analysis was performed using the 2-tailed Fisher exact and Kruskal-Wallis tests. RESULTS: No significant difference was found in the dental or periodontal condition of the 3 groups. The number of teeth, feelings and distal or mesial decay lesions correlated negatively with age, while the number of fixed prosthetic appliances correlated positively. The salivary flow was statistically lower in patients with SS and exhibited a negative correlation with the number of cervical decay lesions. It was also found that SS patients had better oral hygiene habits than subjects of the control groups. CONCLUSIONS: No significant,difference could be detected concerning the dental and periodontal status of SS patients, compared with that of patients with other immune diseases as well as with that of controls who had subjective xerostomia.

Age Factors↗
PubMed2000

Expression of HLA-DR, costimulatory molecules B7-1, B7-2, intercellular adhesion molecule-1 (ICAM-1) and Fas ligand (FasL) on gastric epithelial cells in Helicobacter pylori gastritis; influence of H. pylori eradication.

There is evidence that Helicobacter pylori infection up-regulates the expression of HLA class II molecules by gastric epithelial cells (GEC). In this study we evaluated whether GEC are capable of expression of costimulatory molecules in H. pylori gastritis. The expression of FasL by GEC, before and after eradication of H. pylori, was also studied. Thirty patients (23 men) aged 27-81 years (53.67 +/- 13.99 years (mean +/- s.d.)) with dyspepsia were studied. Upper gastrointestinal endoscopy was performed and six biopsies were obtained (antrum, n = 3; corpus, n = 3) for Campylobacter-Like Organisms (CLO) test and histology; 23 (16 men) were H. pylori+ and seven (all men) were H. pylori- by both methods and served as controls. Helicobacter pylori eradication therapy was given to H. pylori+ patients and all patients were re-endoscoped after 116 +/- 9 days. Formalin-fixed paraffin-embedded tissue sections were stained by the ABC immunoalkaline phosphatase method. In H. pylori gastritis HLA-DR was expressed and correlated with disease activity (P < 0.01). No HLA-DR was observed in controls. In H. pylori-eradicated patients significant decrease of HLA-DR was found (antrum, P < 0. 001). ICAM-1 was expressed by GEC in 80% of H. pylori+ patients; ICAM-1 expression did not correlate with gastritis parameters and decreased significantly after eradication (antrum, P < 0.01). B7-1 and B7-2 were expressed on H. pylori+ samples and their expression decreased after eradication, albeit not significantly. Weak epithelial expression of both B7 molecules was observed in all the controls. FasL was steadily expressed by GEC in both H. pylori+ and H. pylori- patients and remained almost unchanged after eradication. These findings suggest that GEC may acquire antigen-presenting cell properties in H. pylori infection through de novo expression of HLA-DR and costimulatory molecules. This seems to be attenuated after eradication and resolution of mucosal inflammation. The same cells exhibit the capacity to control the inflammatory process, probably by inducing apoptotic cell death to Fas-bearing infiltrating lymphocytes.

Adult↗
PubMed2000

Study of antibody and T cell responses in rabbits immunized with synthetic human B cell epitope analogues of La (SSB) autoantigen.

The aim of this study was to investigate the immunogenicity of four synthetic peptides, representing linear B cell epitopes of the human La/SSB autoantigen: 145-164 aa (p1), 289-308 aa (p2), 301-318 aa (p3) and 349-364 aa (p4), in rabbits. New Zealand White rabbits were immunized with each of the above peptides attached in four copies on tetrameric sequential oligopeptide carriers (SOC) in duplicate. Control immunizations were also performed (one rabbit each, immunized with Freud's complete adjuvant alone or with the SOC carrier alone). Animals were bled at regular intervals and sera were analysed for anti-La/SSB activity by ELISA assays using as antigen the various synthetic peptides, as well as the whole La/SSB protein. Four months after the last immunization, the animals were killed and peripheral blood mononuclear and spleen cells were co-cultured with either the peptides, the SOC carrier, or 27 peptides, covering the entire length of the human La/SSB molecule (23 amino acids long, overlapping by eight residues to each other). A specific, IgG, anti-peptide antibody response was detected, initially directed against the priming peptide, and subsequently expanded to the other La/SSB synthetic peptides. The antibody titres remained high, even 4 months after the last immunization. Sera from rabbits immunized with either p2 or p3 reacted also with the whole La/SSB protein, as was demonstrated by ELISA and immunoblot assays. No reactivities against either Ro60 or Ro52 autoantigen were found. Rabbit spleen cell reacted not only with the epitope used for the immunization but also with other La/SSB peptides. Immunization of rabbits with the major human La/SSB B cell antigenic determinants, linked to SOC carrier, induces strong and sustained antibody and T cell responses against multiple epitopes of the human La/SSB protein. Thus, La/SSB B cell linear epitopes are probably capable also of functioning as T cell epitopes, in this experimental animal.

Amino Acid Sequence↗
PubMed2000

Clinical importance of antibodies against platelet activating factor in antiphospholipid syndrome manifestations.

BACKGROUND: We assessed whether antibodies against platelet activating factor (PAF) are related to the presence of antiphospholipid syndrome (APS) clinical manifestations, in particular thrombosis, in patients with connective tissue diseases. MATERIALS AND METHODS: Anti-PAF, anticardiolipin (aCL), antibeta2 glycoprotein I (antibeta2GPI) and antiphosphatidylcholine (anti-PC) antibodies were determined in 52 patients with APS, 29 patients with systemic lupus erythematosus (SLE) aCL but without APS, 30 patients with SLE without aCL, and 30 patients with scleroderma. A new enzyme-linked immunosorbent assay (ELISA) was developed for determining anti-PAF antibodies in a bovine serum-free fashion. RESULTS: The ELISA showed high specificity. Homologous inhibition experiments showed 60-70% inhibition. Anti-PAF antibodies were found in 18/52 APS patients, 10/29 SLE/aCL+ patients, 9/30 SLE/aCL- patients and 3/30 scleroderma patients. Anti-PAF antibodies were significantly associated with anti-PC antibodies (odds ratio [OR] 12. 7, P < 0.01), and there was a modest association with immunoglobulin G (IgG) aCL (OR 3.1, P > 0.10), but not with IgM aCL or antibeta2GPI. Three SLE/aCL+ patients and five SLE/aCL- patients had clinical manifestations characteristic of APS. All these patients had anti-PAF antibodies, while none had high titres of aCL or antibeta2GPI antibodies and only one had anti-PC antibodies. Among the combined APS and SLE groups, the presence of anti-PAF antibodies was significantly associated with clinical manifestations which are characteristic of APS (OR 2.6, P = 0.02). The effect was independent of IgG aCL and antibeta2GPI antibodies. CONCLUSIONS: Anti-PAF antibodies are common in APS and SLE and comprise an independent factor for the development of thrombosis. Several patients experiencing thromboses have anti-PAF antibodies without other antiphospholipid specificities.

Adult↗
PubMed2000

Remission, relapse, and re-remission of proliferative lupus nephritis treated with cyclophosphamide.

UNLABELLED: Remission, relapse, and re-remission of proliferative lupus nephritis treated with cyclophosphamide. BACKGROUND: Long-term intravenous cyclophosphamide (IVC) in combination with corticosteroids is standard therapy for proliferative lupus nephritis, but it has limitations. There are few data on long-term remission rates, predictors of relapse, and the ability to achieve a second remission with currently recommended IVC regimens. METHODS: A cohort of 85 patients with proliferative lupus glomerulonephritis (focal N = 33, diffuse N = 52) treated with IVC was assembled in three institutions. Timing and predictors of remission, relapse, and re-remission were evaluated with Kaplan-Meier analyses and Cox models. RESULTS: The median time to remission was 10 months, whereas an estimated 22% of patients had not remitted after 2 years. The median time to relapse among 63 patients who had achieved remission was 79 months. In multivariate models, adverse predictors of remission were a delay in the initiation of therapy from the time nephritis was clinically diagnosed [hazard ratio (HR) 0.58, P = 0. 063] and a higher amount of proteinuria (HR 0.86 per 1 g/24 hours, P = 0.014). Predictors of earlier relapse for patients entering remission included a longer time to remission (HR 1.029 per month, P = 0.025), a history of central nervous system involvement (HR 8.41, P = 0.002), and World Health Organization histology (P = 0.01). Among the 23 patients who relapsed during follow-up, the median time to re-remission was 32 months, and with three exceptions, all patients took substantially longer time to remit the second time compared with their first remission (P = 0.01). The time to re-remission was longer in patients who had taken longer to remit the first time (HR 0.979 per month, P = 0.16), in patients who had relapsed earlier after the first remission (HR 1.071 per month, P = 0.002), and in those with evidence of chronicity in the original kidney biopsy (P = 0.015). CONCLUSIONS: Prolonged courses with a cumulative risk of toxicity are needed to achieve remission in many first-treated patients and in most patients treated for a second time. The optimal management of patients with identified adverse predictors of response needs further study.

Cohort Studies↗
PubMed2000

Sjögren's syndrome: autoimmune epithelitis.

Sjögren's syndrome (SS) is a chronic autoimmune disorder of the exocrine glands of unknown aetiology, which is typically associated with focal lymphocytic infiltrates of glandular tissues and autoantibody responses against the Ro(SSA) and La(SSB) ribonucleoproteins. In almost one-third of patients disease involves various extraglandular sites, whereas approximately 5% of patients may also develop malignant B-cell lymphoma. In addition, features of SS are frequently encountered (5-20%) in patients with several other autoimmune rheumatic diseases, and in several respects these 'secondary' forms may be distinct from SS found alone (primary-SS), as well as from each other. The correct diagnosis and management of SS may require consideration from various specialists. Differential diagnosis includes adverse effects of drugs, sarcoidosis, lipoproteinaemias, age-related atrophy, chronic graft-versus-host disease, lymphomas, amyloidosis and infection by human immunodeficiency virus or hepatitis C virus. Based on the sequential application of the validated European classification criteria for SS, a practical algorithm for diagnosis is presented. Despite progress in the understanding of the broad clinicopathological spectrum of the entity, its treatment remains largely empirical and symptomatic. To date, the decision for systemic therapeutic intervention is primarily based on the severity of extraglandular manifestations.

Diagnosis, Differential↗
PubMed2000

Risk factors for central nervous system involvement in systemic lupus erythematosus.

We investigated risk factors for central nervous system (CNS) involvement in systemic lupus erythematosus (SLE), in 32 such patients individually matched 1 : 3 to 96 control SLE patients without CNS events. Univariate analysis showed that CNS involvement was significantly associated with the antiphospholipid syndrome (APS) as well as its features: arterial thrombosis, recurrent fetal loss, livedo reticularis and IgG anticardiolipin (aCL) antibodies in high titres. Other potential associations included cutaneous vasculitic lesions, thrombocytopenia, positive ANA, anti-SS-B/La and low serum levels of C(3) and C(4) complement components, while articular manifestations and discoid rash were significantly less common in patients with neuropsychiatric (NP) disease. In multivariate modeling, CNS involvement was strongly associated with cutaneous vasculitic lesions OR 33, 95% CI 1.5-720) and arterial thromboses (OR 13, 95%CI 0.82-220), and negatively related to the presence of articular manifestations (OR 0.015, 95%CI 0.00-0.17) and discoid rash (OR 0.004, 95%CI 0.00-0.35). Associations with APS-related arterial thromboses and vasculitis point to the importance of arterial vascular pathophysiology in the pathogenesis of NP disease in SLE. Patients with articular manifestations and discoid rash are at very low risk of NP events. Patients with an adverse SLE disease profile may require closer observation and may be the target group for studying pre-emptive interventions.

Adolescent↗
PubMed2000

Prognostic factors and clustering of serious clinical outcomes in antiphospholipid syndrome.

We assessed whether initial clinical presentations suggestive of antiphospholipid syndrome (APS) predicted the subsequent rate and type of serious clinical outcomes. Eighty-two consecutive patients with anticardiolipin antibodies or lupus anticoagulant were followed for 814 person-years after a first event suggestive of APS (livedo reticularis, thrombocytopenia, autoimmune haemolysis, thrombosis, central nervous system manifestations, recurrent abortions). The hazard of developing a second event was largest in patients with antibodies recognizing beta2 glycoprotein I who had autoimmune haemolysis as the first event (hazard ratio HR 2.70, p=0.018) and smallest in patients without such antibodies who had recurrent abortions as their first event (HR 0.37, p=0.028). Subsequent serious events in patients with venous and arterial thromboses, recurrent abortions, central nervous system manifestations and autoimmune haemolytic anaemia were likely to be of the same type as the presenting event (odds ratio (OR) 3.76, 5.90, 77.7, 6.92, and 7.13, respectively. Adjusting for therapy, the rate of subsequent serious events was 6.86-fold higher (p=0.0001) in patients presenting with two events, 1.56-fold higher (p=0.038) in autoimmune haemolysis presentations, 1.69-fold higher (p=0.004) in patients with anti-beta2-glycoprotein-I antibodies, and 46% (p=0.063) lower in thrombocytopenia presentations. Initial clinical features determine the long-term evolution of APS, and specific types of clinical manifestations cluster during the course of the disease.

Adult↗
PubMed2000

Clinically significant and biopsy-documented renal involvement in primary Sjögren syndrome.

Clinically significant renal involvement in patients with primary Sjögren syndrome (pSS) has been described previously only in isolated case reports. The prevalence and significance of the 2 described syndromes, interstitial nephritis (IN) and glomerulonephritis (GMN), are not well known. In a cohort of 471 patients with pSS who were followed for a mean of 10 years, 20 patients (4.2%) developed overt renal disease. Eighteen patients underwent a percutaneous renal biopsy; 2 patients declined. Ten patients had IN, 8 patients had GMN, and 2 patients presented with both entities. Glomerular histology disclosed changes compatible with membranoproliferative GMN in 5 patients and mesangial proliferative GMN in 4 patients. Patients with IN had a younger disease onset compared with patients with GMN (mean, 36.8 compared with 46.0 yr, p 5 0.063). Patients with GMN had longer disease duration compared with patients with IN (mean, 2.2 compared with 8.0 yr, p 5 0.001). The majority of patients with GMN (80%) had mixed monoclonal cryoglobulinemia IgMk (type II) and lower complement C4 levels. Two patients (both with GMN) developed chronic renal failure requiring hemodialysis. Overall, clinically significant renal involvement is infrequent in pSS. IN occurs early in the disease process, while GMN is a late sequela and may have a less favorable prognosis.

Adult↗
PubMed2000

Neuroendocrine manifestations in Sjögren's syndrome. Relation to the neurobiology of stress.

Evidence suggests that autoimmune rheumatic diseases are associated with neuroendocrine dysfunction. Sjögren's syndrome (SS) is proposed as an ideal model to study perturbations in the neuroimmune axis, since patients tend to be medication free and studies are not confounded by the effects of chronic immunosuppressive therapy. The functional integrity of the adrenal, gonadal, and thyroid axes was assessed in SS. Pituitary function of the HPA axis was evaluated directly by determining the ACTH released during oCRH stimulation, while adrenal function was assessed indirectly by endogenous ACTH released during oCRH stimulation. Low basal activity of the HPA axis was associated with pituitary hyporesponsiveness to exogenous CRH, as well as hyporesponsiveness of the adrenal glands to endogenous ACTH. These findings are compatible with a central deficiency of the adrenal axis. An overall attenuated and delayed LH and FSH response to LHRH stimulation was also indicative of central dysfunction of the gonadal axis in SS. SS patients demonstrated elevated basal TSH levels and evidence of mild hypothyroidism. Basal prolactin concentrations were also elevated in SS, and both TSH and PRL showed relatively increased responses to TRH stimulation. The data suggest a central deficiency in all three neuroendocrine axes: adrenal, gonadal, and thyroid. It is not clear if any one system plays a primary role in the expression of the disease. Rather, it is likely that the net effect involves the synergistic and antagonistic effects of multiple hormones. Taken together, adrenal and gondadal steroid hormone deficiency, plus elevated PRL levels, probably greatly affect immune function in SS patients.

Humans↗
PubMed2000

The clinical relevance of antibodies to ribosomal-P common epitope in two targeted systemic lupus erythematosus populations: a large cohort of consecutive patients and patients with active central nervous system disease.

OBJECTIVES: To develop an enzyme linked immunosorbent assay (ELISA) using as substrate a synthetic 22-aminoacid peptide, corresponding to the ribosomal P0, P1 and P2 common epitope. To study the specificity and sensitivity of the method and evaluate the frequency and clinical associations of anti-P antibodies in two groups of systemic lupus erythematosus (SLE) patients: (a) unselected SLE patients and (b) SLE patients with central nervous system (CNS) involvement. PATIENTS AND METHODS: The C-terminal 22 aminoacid peptide of the ribosomal P proteins (Lys-Lys-Glu-Glu-Lys-Lys-Glu-Glu-Lys-Ser-Glu-Glu-Glu-Asp-Glu-Asp-Met- Gly-Phe-Gly-Leu-Phe-Asp) was synthesised according to Merrifield's solid phase procedure. Purification of the peptide was performed by preparative high performance liquid chromatography and confirmed by amino acid analysis. Using this peptide, in a concentration 5 microg/ml, an ELISA was developed. The presence of anti-P antibodies was evaluated by western blot using purified ribosomal proteins from rat liver. Sera from 178 consecutive patients with SLE and 28 patients with SLE and CNS manifestations were tested. Sera from 58 patients with rheumatoid arthritis and 57 patients with primary Sjögren's syndrome were used as controls. The cut off point of the assay was defined using 124 normal sera. RESULTS: The specificity of the assay was evaluated by homologous inhibition. Pretreatment of positive sera with soluble 22mer peptide of the ribosomal P proteins resulted in 88% inhibition. The concordance between the peptide assay and western blot was found to be 83%. Thirty three of 178 (18. 6%) of the unselected SLE patients had antibodies to P-protein common epitope. Their presence was associated with more active disease (European Consensus Lupus Activity Measurement, ECLAM scoring system) (p<0.001), higher levels of anti-ds DNA antibodies (p<0.05) and lower levels of the C4 component of complement (p<0.01). Eleven of 28 (39.3%) patients with SLE and active CNS involvement had antibodies to P-protein. The overall prevalence of anti-P antibodies in active CNS disease patients was statistically significantly higher, as compared with unselected SLE patients (chi(2)=6.04, p<0.05). These antibodies were found in a high proportion of patients without anticardiolipin antibodies (52.4%) and they were associated with diffuse CNS involvement (psychiatric disorders (71%) and epilepsy (75%)). CONCLUSIONS: A synthetic analogue of the common epitope of ribosomal P-proteins can be use as an antigen for the detection of anti-P antibodies. These antibodies are associated with active SLE and CNS involvement particularly in patients without anticardiolipin antibodies.

Adult↗
PubMed2000

Anaemia in systemic lupus erythematosus: aetiological profile and the role of erythropoietin.

OBJECTIVE: To study the prevalence of different causes of anaemia in patients with systemic lupus erythematosus (SLE) and their associations with immunological and clinical parameters and to evaluate the contribution of erythropoietin (Epo) and anti-erythropoietin (anti-Epo) autoantibodies to the development of SLE anaemia. METHODS: 132 SLE patients with anaemia (defined as haemoglobin of 12 g/dl or less for women and 13.5 g/dl or less for men) from among a total of 345 consecutive SLE patients were prospectively enrolled into the study. Standard haematological and immunological tests were performed and serum Epo and anti-Epo antibodies were assayed. RESULTS: The identified causes were anaemia of chronic disease (ACD) n=49 (37.1%), iron deficiency anaemia (IDA) n = 47 (35.6%), autoimmune haemolytic anaemia (AHA) n = 19 (14.4%) and other causes n = 17 (12.9%). There was significant heterogeneity in the severity of anaemia between the four groups (p<0.01) with AHA cases being on average more severe. The proportion of patients with anticardiolipin antibodies, low complement levels and anti-dsDNA differed significantly among the four groups; these markers were particularly common in patients with AHA, and uncommon in patients with IDA. Twenty one of 100 tested patients had anti-Epo antibodies. Such antibodies were seen practically only in patients with ACD (odds ratio 3.1, p = 0.041) and in patients with high lupus activity (ECLAM) scores (odds ratio 1.27 per point, p = 0.055). Epo response was inadequate in 42.4% and 41.2% of patients with ACD and AHA, respectively. CONCLUSIONS: Anaemia in SLE usually takes the form of ACD and IDA, however autoimmune haemolysis is not uncommon. SLE patients with different causes of anaemia differ in regard to several immunological parameters. Epo response is blunted in anaemic SLE patients, particularly those with ACD and AHA.

Adult↗
PubMed2000

Systemic scleroderma in Greece: low mortality and strong linkage with HLA-DRB1*1104 allele.

OBJECTIVE: Description of Greek patients with scleroderma with reference to (a) major organ disease, (b) autoantibodies, (c) survival rate, and (d) HLA associations. METHODS: The clinical files of 254 patients were analysed retrospectively and a standardised clinical chart was completed with age at disease onset, sex, date of first and last visit, clinical and serological findings, organs affected, reasons for death, and HLA class II alleles. HLA class II alleles (DRB1, DQA1, DQB1, DPB1) were determined by polymerase chain reaction amplification using oligopeptide probes. DNA was extracted from 98 patients and 130 Greek controls. RESULTS: 124 patients (49%) had limited systemic sclerosis (lSSc), 114 (45%) had diffuse systemic sclerosis (dSSc), and 16 (6%) had overlap syndromes. Patients with dSSc, compared with lSSc, were characterised by a higher prevalence of lung disease (p=0.0011), oesophageal, heart, and peripheral vessel disease (p=0.027, p=0.0025, and p=0.012, respectively). Anticentromere antibodies (ACA) occurred exclusively in lSSc (34%), whereas antibodies to topoisomerase I (anti-topo I) were associated with dSSc (p<0.0001). Anti-topo I were associated with interstitial pulmonary fibrosis, oesophageal and peripheral vessel disease (p=0.028, p=0.012, and p=0.01, respectively). The HLA-DRB1*1104 allele was associated with the disease (p<0.0001) and anti-topo I (p<0.001), whereas it was not associated with ACA serum reactivity (p<0.001). Renal disease occurred in 4% of patients with SSc. The estimated survival probability for this cohort of patients with SSc, four years after the first visit, is 94.8%. CONCLUSION: SSc among Greek subjects has the same pattern of organ disease as in other white populations. However, the prevalence of kidney disease is low. The HLA class II DRB1*1104 allele is associated with the disease, with anti-topo I, and not associated with ACA serum reactivity.

Adult↗