[The role of HLA-B27 molecules in the pathogenesis of ankylosing spondylitis]. / Il ruolo delle molecole HLA-B27 nella patogenesi della spondilite anchilosante.

Ankylosing Spondylitis (AS) is characterised by the strongest association with an HLA antigen ever described for any disease. It represents therefore the ideal model for the understanding of the link between immune-mediated diseases and the HLA system. The role of HLA-B27 in the pathogenesis of AS will be discussed focusing on the recently described higher expression of these molecules in patients with AS compared with healthy controls.

Increased pulmonary epithelial permeability in systemic sclerosis is associated with enhanced cutaneous nerve growth factor expression.

Background: Nerve growth factor (NGF), a neurotrophic factor that indirectly induces fibroblast proliferation and collagen production, has been found to be increased in the affected dermis of patients with systemic sclerosis (SSc). To investigate the possibility of a relationship between cutaneous NGF production and pulmonary damage in SSc, we studied seven non-smoking scleroderma patients. Methods: Abnormalities in lung structure were assessed by radiological lung examination, and pulmonary epithelial permeability (PEP) was determined by ventilation lung scintigraphy. All patients underwent skin punch biopsy with NGF immunohistological staining. Results: A statistically significant correlation was found between the PEP values and the cutaneous NGF staining scores, which were markedly increased in all of the patients examined, irrespective of the age, disease duration, or radiologically defined lung abnormalities. Conclusion: These results support the hypothesis that functional and anatomical changes in SSc target organs may be determined by a local tissue hyperproduction of NGF.

Tracheo-bronchial mucociliary clearance in patients with primary and secondary Sjögren's syndrome.

We determined the tracheo-bronchial mucociliary clearance (MCC) in order to evaluate a possible impairment of this function in patients affected by Sjögren's syndrome (SS) with or without overt clinical symptoms of xerotrachea. The MCC was expressed as flow rate (mm/min) and studied in 22 non-smoking SS patients (10 pSS and 12 sSS) and in 8 control subjects by specifically adapted ventilation lung scintigraphy (VLS). The MCC in the control group was 5.9 +/- 1.1 mm/min. No values were produced for MCC in 16 SS patients (8 pSS and 8 sSS) in the time interval considered and were reduced in the remaining 6 SS patients (3.3 +/- 1.2 mm/min). In all nine cases with clinical evidence of xerotrachea no values for MCC were obtained. A significant correlation was found between the MCC values and the rate of stimulated salivary excretion determined by dynamic scialoscintigraphy in the same patients (p < 0.001). These preliminary data show that the majority of SS patients studied presented with MCC impairment, always found when clinical symptoms of xerotrachea were present.

Abnormalities of magnetic resonance imaging of the central nervous system in patients with systemic lupus erythematosus correlate with disease severity.

Forty randomly selected patients with systemic lupus erythematosus (SLE) were studied by clinical and serologic parameters and magnetic resonance imaging (MRI). Abnormal MRI was found in 15/40 patients (37.5%): all 15 cases showed multiple widespread small-sized areas of increased signal in T2 in the white matter; in one of these patients MRI also displayed a large area with a reduced signal in T1 and an increased signal in T2 involving both the white and the gray matter. Among the 15 patients with abnormal MRI, only 7 had neuropsychiatric symptoms. The presence of MRI changes was highest in patients with organic type symptoms and was associated to the highest disease severity scores. A long-term follow up of asymptomatic patients would be useful to establish whether the application of MRI is appropriate for the assessment of CNS involvement in SLE.

Circulating antibodies to DNA-related antigens in patients with autoimmune thyroid disorders.

A high prevalence of antibodies to double-stranded DNA (AbDNAds) has been recently reported in serum of patients with autoimmune thyroid disorders, but the specificity of this finding has been questioned. For this reason, the prevalence of several antibodies to DNA-related nuclear antigens (AbDRENA) has been evaluated in sera of patients with autoimmune and non-autoimmune thyroid disease. The study group included: 46 Graves' disease patients, 28 Hashimoto's thyroiditis patients, 25 patients with toxic nodular goitre and 11 with non-toxic nodular goitre. Twenty-eight Graves' patients were retested during methimazole (MMI) therapy, and 5 after radioiodine administration. Twenty-two patients with systemic lupus erythematosus and 28 normal subjects served as positive and negative controls, respectively. AbDRENA included: AbDNAds by RIA or immunofluorescence (IF); antibodies to single-stranded DNA (AbDNAss) and antibodies to histone (AbHist) by ELISA methods; antibodies to nuclear antigens (ANA) by immunofluorescence. RIA values were considered to be abnormal when 2 SD above the mean of normal controls. In our study 13% of Graves' patients were positive for AbDNAds by RIA: all of them had negative tests by IF; 11% were positive for AbDNAss, 2% for AbHist and 7% for ANA. A comparable prevalence of positive results for AbDNAds by RIA, with negative IF tests, was found in Hashimoto's thyroiditis patients. No significant changes of antibody levels were observed in Graves' patients during MMI treatment or after radioiodine administration. A positivity for AbDNAds or AbDNAss was found in 8% of patients with toxic nodular goitre, but in none of those with non-toxic goitre.(ABSTRACT TRUNCATED AT 250 WORDS)

Development of thyroid disease in patients with primary and secondary Sjögren's syndrome.

Autoimmune thyroid disease associated to Sjögren syndrome (SS) may be defined by serological and functional abnormalities. We studied the prevalence of serum anti-thyroid autoantibodies and the development of thyroid functional defects by a follow-up investigation in patients with primary (pSS) and secondary SS (sSS). In keeping with previous literature data, our findings confirmed an increased prevalence of thyroid autoimmune phenomena in the whole series of patients with SS. In addition, evidence was provided for a greater incidence of serological and functional thyroid abnormalities in pSS when compared to sSS. Follow-up study also showed that the rate of thyroid autoimmune disease development was higher in pSS than in sSS. The appearance of circulating anti-thyroid antibodies was particularly frequent in patients with preexisting antibodies against extractable nuclear antigens (anti-ENA). These data indicate the need for a careful monitoring of thyroid function in SS patients, with particular regard to those with pSS and positive anti-ENA tests.

The efficacy and safety of auranofin in the treatment of juvenile rheumatoid arthritis. A long-term open study.

The safety and efficacy of auranofin in the long-term treatment of children with juvenile rheumatoid arthritis was investigated in an open study of 14 patients. Twelve patients completed at least 12 months of treatment, and 7 patients completed 36 months of treatment. Classic parameters of disease activity showed improvement over baseline values after 6 months of treatment, and laboratory indices remained stable or improved throughout the study. Auranofin was well tolerated; the frequency of adverse effects was lower in these patients than has been previously reported in either adults or children whose arthritis has been treated with injectable gold.

Long-term follow-up of technetium articular index in rheumatoid arthritis patients during oral chrysotherapy: evidence of paradoxical behaviour.

The Technetium Articular Index (TcAI) is regarded as a parameter of local inflammation in rheumatoid arthritis (RA). We studied TcAI behaviour during 1-year chrysotherapy in a group of fifteen RA patients. In non-responders TcAI showed a gradual decrease up to the 6th month and a return to baseline values within the second semester of the follow-up; conversely, in response patients TcAI remained unchanged during the entire period of the study, thus showing a paradoxical behaviour probably depending on the recovery of normal physical ability and articular activity.

Lack of corneal chrysiasis in rheumatoid arthritis patients undergoing oral gold therapy.

Corneal chrysiasis is a common consequence of parenteral chrysotherapy in patients affected by rheumatoid arthritis. Concerning the factors and conditions that could be determinant for the gold accumulation in the cornea, there are contradictory opinions. Total or weekly gold dose and its accumulation quota, and the frequency of drug administration, seemed to be parameters to which corneal chrysiasis could be related. Since all these parameters are completely different during oral gold therapy, previous investigations on corneal chrysiasis are inapplicable to patients undergoing oral treatment. This study, performed on rheumatoid arthritis patients treated with auranofin, orally administered for 8-34 months, did not reveal any appreciable corneal deposits of gold.

[Psoriatic arthritis: considerations on recent studies: serum beta 2 microglobulin and circulating T-gamma lymphocytes]. / Artrite psoriasica: considerazioni su recenti acquisizioni: la beta 2 microglobulina sierica e i linfociti T gamma circolanti.

The results of two recent studies of our group have been reported. They regard two immunological parameters of psoriatic arthritis: the proportions of T gamma lymphocytes in peripheral blood and the beta 2 microglobulin in the serum. The data obtained in psoriatic arthritis patients have been compared to those found in normal controls and in rheumatoid arthritis patients. T gamma mean values in psoriatic arthritis were significantly lower than those present in healthy subjects and in rheumatoid patients. These last patients showed beta 2 microglobulin mean values significantly higher than those observed in normal controls and in psoriatic arthritis patients. Conversely, the mean of beta 2 microglobulin levels in psoriatic arthritis has been found to be similar to that observed in normal controls, but a superimposition in the range of individual values of these two groups with the concentrations determined in rheumatoid subjects has been found. These results seem to be of interest in relation to the immunopathogenetic mechanism of psoriatic arthritis, but are of little help in the clinical differentiation of the two rheumatological affections considered.

Peripheral blood T lymphocyte subpopulations defined by monoclonal antibodies in rheumatoid arthritis: distribution in patients untreated and treated by oral gold therapy.

The distribution of T lymphocyte subsets was determined in peripheral blood (PB) of two groups of patients with rheumatoid arthritis by using monoclonal antibodies (OKT). In untreated patients the percentage of OKT4+ cells (helper/inducer) was found to be significantly increased as compared to healthy controls. In patients receiving oral gold therapy a similar increase in OKT4+ cells was confirmed; furthermore, these patients showed a significant decrease in OKT8+ cell population (cytotoxic/suppressor) compared to untreated patients and to normal controls. A small numerical superimposition of values of OKT4+ and OKT8+ lymphocytes was observed in untreated but not in treated patients.