Novel biomarkers for the assessment of paediatric systemic lupus erythematosus nephritis.

The discovery of serum biomarkers specific for paediatric lupus nephritis (pLN) will facilitate the non-invasive diagnosis, follow-up and more appropriate use of treatment. The aim of this study was to explore the role of serum high-mobility group box 1 (HMGB1) protein, antibodies against nucleosomes (anti-NCS), complement factor C1q (anti-C1q) and glomerular basement membrane (anti-GBM) in pLN. Serum samples of 42 patients with paediatric systemic lupus erythematosus (pSLE) (22 with pLN and 20 without renal involvement), 15 patients with other autoimmune nephritis (AN) and 26 healthy controls (HCs) were examined using enzyme-linked immunosorbent assay (ELISA). The activity of both pSLE and pLN was assessed by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) tool. The levels of all four biomarkers were significantly higher in pLN compared to AN and to HCs. The anti-NCS, anti-GBM and HMGB1 serum levels were significantly higher in pLN than in pSLE without renal involvement. The anti-C1q and the HMGB1 serum levels were correlated positively with pSLE activity. The HMGB1 serum levels were also correlated positively with pLN activity. These findings suggest that serum anti-NCS, anti-GBM and HMGB1 may serve as biomarkers specific for the presence of nephritis in pSLE. HMGB1 emerged as a useful biomarker for the assessment of pLN and pSLE activity, whereas anti-C1q only of pSLE activity.

Clinical expression and course in patients with late onset systemic lupus erythematosus.

BACKGROUND: To analyze the pattern of clinical expression and the 5-year disease course in Caucasian patients with late onset of systemic lupus erythematosus (SLE) and to compare the findings with an early onset SLE group. METHODS: Medical records of 551 patients who presented with SLE at hospitals of the region of Thessaloniki between 1989 and 2007 were studied. Patients who developed SLE at or after the age of 50 years were classified as the late onset group, while younger patients served as the early onset group. Data on clinical manifestations and damage accrual at disease onset and at 5 years was obtained and compared between the two groups. RESULTS: In 121 patients, the disease started after the age of 50 years. Elderly patients showed less pronounced female predominance and less often presented with malar rash, nephropathy, fever and lymphadenopathy, while lung involvement, pericarditis and sicca syndrome were more frequent. Damage accrual was similar in both groups. The main causes of damage at 5 years differed, with the elderly exhibiting more cardiovascular damage. They also had a higher incidence of hypertension and osteoporosis at 5 years. CONCLUSIONS: Caucasian SLE patients with late onset of the disease present with different clinical manifestations, suggesting that age affects the expression of SLE. Damage accrual at 5 years is similar in the elderly and the younger patients. However, the causes of this damage and the occurrence of other comorbidities follow a different pattern, possibly reflecting the disease process and the effects of aging.

Clinical expression and morbidity of systemic lupus erythematosus during a post-diagnostic 5-year follow-up: a male:female comparison.

The aim of this study was to analyse the prevalence of the most relevant clinical features of the diagnosis of systemic lupus erythematosus (SLE) in a sample of male patients with lupus as well as the incidence of the main causes of morbidity in a 5-year period after the diagnosis. A further aim of this study was to investigate the impact of gender on expression and morbidity of SLE. Data were collected from the medical records of 59 male and 535 female patients with SLE who were diagnosed at the hospitals in the region of Thessaloniki. Several differences in the expression and morbidity of the disease were found in relation to the gender of the patient. Male patients had a higher prevalence of thromboses, nephropathy, strokes, gastrointestinal tract symptoms and antiphospholipid syndrome when compared with female patients, but tended to present less often with arthralgia, hair loss, Raynaud's phenomenon and photosensitivity as the initial clinical manifestations. During the 5-year follow-up, positive associations have been found between male gender and the incidence of tendonitis, myositis, nephropathy and infections, particularly of the respiratory tract. In conclusion, this study has provided information regarding the features of clinical expression and morbidity in male patients, and has shown that gender is a possible factor that can influence the clinical expression of SLE.

Evaluation of the Greek version of the Bath Ankylosing Spondylitis Functional Index: reliability, validity, and factor analysis.

OBJECTIVE: To translate the Bath Ankylosing Spondylitis Functional Index (BASFI) into Greek, and validate its psychometric properties for the Greek patient population. Also, to assess the degree to which questions in the scale did address common themes, using confirmatory factor analysis. METHODS: BASFI has been translated into Greek (BASFI-GrV), applied to 61 patients with ankylosing spondylitis, and validated as follows: a) Cronbach's alpha for the estimation of the internal consistency. b) Spearman's correlation coefficient for the assessment of test-retest reliability. c) Spearman's correlation coefficient for the assessment of concurent validity against the Hospital Anxiety and Depression Scale (HADS). d) Factor analysis. RESULTS: The results showed the following: a) The BASFI-GrV demonstrated good internal consistency (alpha: 0.75). b) Test-retest scores produced no significant difference (p = 0.07). Spearman's rho correlation coefficient for test-retest was high on average (r = 0.91, p < 0.001), and ranged from 0.56 to 0.94 for each item. c) Spearman's rho between BASFI-GrV and HADS was 0.43 (p < 0.001). d) Factor analysis identified three factors with Eigen values ranging from 1.01 to 4.71, explaining totally 67.9 % of the variance. CONCLUSION: Our findings indicate that BASFI-GrV is a valid and reliable questionnaire that can be used to evaluate the functional status of Greek patients with ankylosing spondylitis.

Mixed cryoglobulinemia in Greece. Primary disorders in 10 cases.

Mixed cryoglobulinemia (MC) is a systemic disorder whose pathogenesis is based on the presence of serum cryoglobulins. The purpose of this study was to evaluate on a prospective basis patients presenting with MC with regard to the clinical manifestations and the underlying disorders. We present ten patients with MC, who were diagnosed and followed up during a one year period in the Division of autoimmune rheumatic diseases (Clinical Department of Pathophysiology). MC was associated with hepatitis C virus (HCV) infection in two cases, with hepatitis B virus (HBV) infection in six, one patient had both HCV and evidence of HBV infection, while the remaining three patients fulfilled European classification criteria for diagnosis of Sjögren's syndrome (SS). In all ten cases, the presence of an underlying factor was identified, being either viral or autoimmune. It is concluded therefore that all patients presenting with MC should be completely evaluated for a hepatitis virus infection or an autoimmune or lymphoproliferative disorder. Furthermore, since the initiation of the process of MC is triggered by many factors, research should be directed towards the identification of the underlying common denominator.

D-penicillamine induced myasthenia gravis: clinical, serological and genetic findings.

Eight cases of D-penicillamine (DP) induced myasthenia gravis (MG) are presented. Seven patients were being treated for rheumatoid arthritis (RA) and one for scleroderma. The mean duration of DP treatment until the myasthenic symptoms developed ranged from 2-8 months. The DP dose reached 500 mg daily. It was found that the clinical and immunological findings were almost similar to those of idiopathic MG, but were less severe. All patients had increased titers of acetylcholine receptor antibodies in their sera. Discontinuation of D-penicillamine resulted in the complete resolution of myasthenic symptoms after 2-6 months. One patient required ventilation, immunosuppressive therapy and plasma exchange. No association was found between DP related MG and the various autoantibodies tested. Immunogenetic analysis showed that three patients had HLA-DR1, two HLA-DR3, one HLA-DR4 and one HLA-DR5. In conclusion, the clinical presentation of DP-induced MG seems similar to idiopathic MG. DP-related MG is relatively benign, although it sometimes can cause life-threatening muscle weakness requiring aggressive therapy. The relatively small number of patients included in this study, however, does not permit any firm conclusions regarding the HLA associations of DP-related MG.

Alveolitis correlates with clinical pulmonary involvement in primary Sjögren's syndrome.

Bronchoalveolar lavage (BAL) was performed in 23 patients with primary Sjögren's syndrome (1Ss) and ten healthy controls to evaluate alveolitis and correlate it with pulmonary and systemic manifestations. Patients with 1Ss had higher BAL total cell count (9.2 +/- 6.7 millions/ml vs 6.1 +/- 2.9 millions/ml) and higher percentage of lymphocytes 23.3 +/- 15.6 percent vs 6.5 +/- 2.9 percent, p less than 0.001) than controls. Twelve patients (group A) constituted the "high alveolitis" group (lymphocytes greater than 15.2 percent) and ten (group B) constituted the "low alveolitis" group (lymphocytes less than 15.2 percent). Group A had more frequent cough (6/12 vs 2/10, p = 0.07), dyspnea (4/12 vs 1/10), and roentgenologic evidence of interstitial lung disease (5/12 vs 0/10, p less than 0.05). They also had lower total lung capacity (85.6 +/- 14.2 percent pred vs 105.8 +/- 23.3 percent pred, p less than 0.05) and Dco (87.7 +/- 20.6 percent pred vs 103.6 +/- 21.0 percent pred). All patients with +3 or +4 grading or lymphocytic infiltrates in lip biopsy specimen belonged in group A (5/12). Finally, T-helper/T-suppressor ratio was lower in group A than in group B. The intensity of alveolitis was not correlated with clinical or serologic manifestations of systemic disease.

T cell subpopulations in the labial minor salivary gland histopathologic lesion of Sjögren's syndrome.

The majority of T cells constituting the focal lymphocytic infiltrates in the labial minor salivary glands of patients with Sjögren's syndrome bear the helper phenotype (CD4); activation is expressed by class II (HLA-DR) MHC products. In our immunohistologic study of snap frozen minor salivary gland biopsies from 16 patients with primary Sjögren's syndrome, it was shown that the majority (77%) of the infiltrating T cells exhibit the memory helper/inducer phenotype (UCHL-1) and express LFA-1 molecules. In addition most of the T cells express the alpha beta receptor while only 2.8% express the gamma delta receptor. Our findings suggest that these T cell infiltrates in patients with primary Sjögren's syndrome may explain the intense B lymphocyte hyperreactivity observed in the exocrine glands of patients with Sjögren's syndrome.

Monoclonal process in primary Sjögren's syndrome and cross-reactive idiotype associated with rheumatoid factor.

Monoclonal or oligoclonal B cell products have been described in the sera and urine of patients with primary Sjögren's syndrome (PSS). In addition, monoclonal expansion of plasma cells has been found in the exocrine glands of PSS patients with circulating monoclonal B cell products. The goal of this study was to raise an anti-idiotype to a cryoprecipitable monoclonal IgM kappa rheumatoid factor (RF) from a PSS patient. Using the F(ab')2 fragments of the rabbit IgG anti-idiotype, an idiotype-specific ELISA was developed and sera from 32 patients with PSS (13 with monoclonal IgM kappa), 33 with rheumatoid arthritis, three with rheumatoid arthritis + Sjögren's syndrome (SS), 30 with systemic lupus erythematosus, six with Waldenström's macroglobulinaemia, and 20 healthy controls were tested. The idiotype was primarily found in PSS patients with circulating monoclonal IgM kappa and more often in those who had a ratio of kappa: lambda intracytoplasmically positive plasma cells greater than 3:1 in the lymphocytic infiltrates of minor salivary glands, and systemic manifestations. The idiotype was also found in PSS and rheumatoid arthritis patients without circulating monoclonal cryoglobulins as well as in two of the six patients with Waldenstrom's macroglobulinaemia. Our results suggest that the monoclonal process observed in PSS could involve restricted idiotypic clones that are susceptible to malignant transformation.

Raynaud's phenomenon in primary Sjögren's syndrome.

Our study describes the prevalence, clinical picture, course and sequelae of Raynaud's phenomenon in patients with primary Sjögren's syndrome. Furthermore, our study compares the clinical, serologic and immunogenetic profile of patients with Raynaud's phenomenon versus those without Raynaud's phenomenon. It seems that Raynaud's phenomenon is a common manifestation (33%) in patients with primary Sjögren's syndrome, precedes sicca manifestations in 42% of patients and follows a pleomorphic course; in some patients (14%) it disappears during the course of Sjögren's syndrome, in others (30%) the frequency of attacks decreases while in a 3rd group (56%) it remains the same. The local clinical sequelae of Raynaud's phenomenon in patients with primary Sjögren's syndrome are swollen hands and evidence of small, soft tissue calcifications on radiographs. Digital pulp ulcers, sclerodactyly or periungal telengiectases are not seen. It seems however, that patients with primary Sjögren's syndrome and Raynaud's phenomenon develop glomerulonephritis, myositis and peripheral neuropathy more often than patients without Raynaud's phenomenon. These differences however, had no statistical significance. Finally, the autoantibody profile is similar in patients with and without Raynaud's phenomenon, while patients without Raynaud's phenomenon and primary Sjögren's syndrome showed a negative but not statistically significant association with the HLA-DR4 alloantigen.

Pulmonary function of nonsmoking patients with systemic lupus erythematosus.

The pulmonary function of 70 nonsmoking patients with systemic lupus erythematosus (SLE) was evaluated, and the results were compared with those of 70 age- and sex-matched, nonsmoking healthy individuals. Isolated reduction of carbon monoxide diffusing lung capacity (DCO), usually subclinical, was the most commonly detected functional abnormality in the SLE population, whereas it was absent in the comparison group. Isolated small airways disease (SAD) was observed in a relatively high percentage of patients, but not significantly different from that in the healthy people. Restrictive and obstructive patterns were very unusual in the SLE people and absent in the members of the comparison group. Finally, normal lung function was seen in the majority of the latter, but only in one third of the lupus patients. Subclinical respiratory dysfunction, most commonly expressed as diminished DCO, is a common feature of SLE.

Pulmonary function of nonsmoking patients with giant cell arteritis and/or polymyalgia rheumatica; a controlled study.

The pulmonary function of 26 nonsmoking patients with giant cell arteritis (GCA) and/or polymyalgia rheumatica (PMR) was evaluated and the results were compared with those of 28 age and sex matched nonsmoking controls. Normal function was observed in 30.8% of the patients and 50% of the controls (p = non significant). Isolated small airways disease (SAD) was detected in a high percentage of the patients (46.2%), but not significantly different from that of the controls (50%). Its clinical significance remains to be answered. Obstructive, restrictive and diffuse interstitial lung disease (DILD) was seen in one, three and two patients respectively, but was absent in the control population. All the patients had a normal chest radiograph and were asymptomatic, except for three. Two of them had normal respiratory function and one DILD. It is speculated that DILD and restrictive disease, seen only in patients with biopsy proven GCA, may be related to the underlying process.

Nandrolone decanoate (deca-durabolin) in primary Sjögren's syndrome: a double blind pilot study.

The efficacy and side-effects of Deca-Durabolin (DD) were tested, in a double blind fashion, in twenty female primary Sjögren's syndrome (1 degree SS) patients. Ten randomly assigned patients received DD (100 mg IM bi-weekly) for six months, and ten others placebo, for the same period. Analysis of the results revealed that the DD-treated patients showed a moderate improvement of subjective xerostomia, a significant decrease of the erythrocyte sedimentation rate (ESR), and an overall improvement of their feeling of well-being, -judged by themselves and the investigator subjectively-, when compared with the placebo group. All the sicca objective parameters (results of Schirmer's I test, slit lamp eye examination after rose bengal staining, stimulated parotid flow rate measurements and labial minor salivary gland histopathology) were not significantly altered in either group. The clinical side-effects were the expected ones, i.e. hirsutism, hoarseness and an increase in libido, more pronounced in the DD-treated group. At the end of the study, one DD-treated patient, developed a diffuse well-differentiated B-lymphocytic lymphoma, which regressed spontaneously three months later.

Rheumatoid arthritis in Greece. Manifestations in different age groups.

A high frequency of anti-Ro (SSA) circulating antibodies and lack of HLA-DR4 association described recently in Greek rheumatoid arthritis (RA) patients, prompted us to study their clinical and laboratory picture and compare it with that described in the literature. One hundred and ninety seven patients with definite or classical RA were divided into three groups A, B, and C with age at disease onset below 39, between 40 and 59, and above 60 years respectively. Disease duration below 5 and above 5 years resulted in further division of each group into subgroups 1 and 2. With few exceptions, there were no significant differences between the groups in terms of maximal articular index, lymphadenopathy, splenomegaly, hepatomegaly, frequency of rheumatoid nodules and lowest hematocrit, highest erythrocyte sedimentation rate, and C-reactive protein values. The presence of rheumatoid factor, antinuclear antibodies, cryoglobulins, and elevated levels of globulins, C3 and C4 in patients' sera were not significantly different among the groups. A statistically significant radiologic deterioration was observed with disease duration, common in all groups. Diffuse interstitial lung disease was the most common pulmonary abnormality noted. There were no differences between the groups. Penicillamine toxicity was independent of age and disease duration. This study suggests that the clinical picture of RA in Greece is similar to that in other populations and that there are no significant differences in general among its age groups.

Cyclosporin a therapy in patients with primary Sjögren's syndrome: results at one year.

We present our experience with small doses of cyclosporine A (CyA), 5 mg/kg/day, in patients with primary Sjögren's syndrome treated for up to 12 months. Subjective improvement in xerostomia occurred at 6 months of treatment, without objective improvement in any sicca parameters. At 12 months, xerostomia improved slightly, but minor salivary gland histology worsened. We conclude that small doses of CyA in patients with primary Sjögren's syndrome for up to 12 months are rather ineffective.