Pier Franca Gambari

Risk of congenital complete heart block in newborns of mothers with anti-Ro/SSA antibodies detected by counterimmunoelectrophoresis:. A prospective study of 100 women.

OBJECTIVE To assess the true prevalence of congenital complete heart block (CCHB) in infants of anti-Ro/SSA-positive women known to have connective tissue disease (CTD) and, secondarily, to evaluate the prevalence of other electrocardiographic abnormalities in these newborns at birth. METHODS A prospective study was conducted in 4 referral hospitals. One hundred anti-Ro/SSAA-positive mothers were followed up before they became pregnant and during the index pregnancy. Counterimmunoelectrophoresis and immunoblotting were used to test for antibodies to extractable nuclear antigens. RESULTS Of the 100 women with anti-Ro/SSA antibodies, 2 had infants who developed CCHB in utero (2%). The CCHB was detected at 22 weeks and 20 weeks, respectively. One of the 2 mothers had primary Sjögrens syndrome (SS), and the other had undifferentiated CTD (UCTD). No case of CCHB occurred among the infants of 53 mothers with systemic lupus erythematosus (SLE). No fetal death occurred due to CCHB. In 2 centers, electrocardiography was recorded in 24 unselected newborns, and 4 were found to have sinus bradycardia. CONCLUSION The prevalence of CCHB in newborns of prospectively followed up women already known to be anti-Ro/SSA positive and with known CTD was 2%. This finding is useful with regard to preconception counseling of these women. The risk of delivering an infant with CCHB may be higher in mothers with primary SS or UCTD than in those with SLE. Additional electrocardiographic abnormalities such as sinus bradycardia and prolongation of the QT interval may be present in their children.

Risk factors for subclinical atherosclerosis in a prospective cohort of patients with systemic lupus erythematosus.

Objective: To evaluate traditional and non-traditional risk factors for subclinical atherosclerosis in systemic lupus erythematosus (SLE). Methods: A prospective cohort of 78 patients with SLE without overt atherosclerotic disease was studied. SLE clinical and laboratory parameters, disease activity and damage, treatment and traditional risk factors for atherosclerosis were evaluated. At baseline (T1) and after five years’ follow up (T2), the serum levels of anti-oxidised palmitoyl arachidonoyl phosphocholine (oxPAPC), anti-heat shock protein 65, and anti-β2-glycoprotein I antibodies and C reactive protein were tested. At T2, intima-media thickness (IMT) was measured using duplex carotid sonography. Thickened intima, plaque, mean IMT (m-IMT), and maximum IMT (M-IMT) were assessed. Results: A thickened intima was seen in 22/78 (28%) patients and plaque in 13/78 (17%). M-IMT and m-IMT were (mean (SD)) 0.77 (0.34) mm and 0.55 (0.15) mm, respectively. Patients with carotid abnormalities were significantly older, had higher blood pressure and total serum cholesterol levels, and had taken a higher prednisone cumulative dosage than those without any lesions. The carotid abnormalities were associated with renal disease and ECLAM >2 at T1, and with azathioprine treatment. In multivariate analysis, age and cumulative prednisone dose were associated with carotid abnormalities; age, hypertension, and anti-oxPAPC at T2 were correlated with higher M-IMT and m-IMT. Conclusions: In patients with SLE some non-traditional risk factors for atherosclerosis were identified, the most important of which was the cumulative prednisone dose. The role of some traditional risk factors, such as age and hypertension, was also confirmed. The predictive value of the new immunological and inflammatory markers of atherosclerosis seems to be masked by some disease related features.

Pregnancy outcome in 100 women with autoimmune diseases and anti-Ro=SSA antibodies: a prospective controlled study

Anti-Ro/SSA antibodies are associated with neonatal lupus but are also considered a possible cause for unexplainedpregnancy loss and adverse pregnancy outcome. In a large multicentres cohort study we have prospectivelyfollowed 100 anti-Ro/SSA positivewomen (53 systemic lupus erythematosus (SLE)) during their 122 pregnancies and 107 anti-Ro/SSA negative women (58 SLE) (140 pregnancies).Anti-Ro/SSA antibodies were tested by immunoblot and counterimmunoelectrophoresis. Mean gestational age at delivery (38 vs 37.9 weeks), prevalence of pregnancy loss (9.9 vs 18.6%), preterm birth (21.3 vs 13.9%), cesarean sections (49.2 vs 53.4%), premature rupture of membranes(4.9 vs 8.1%), preeclampsia(6.6 vs 8.1%), intrauterinegrowth retardation(0 vs 2.3%) and newborns small for gestationalage (11.5 vs 5.8%) were similar in anti-Ro/SSA positive and negative SLE mothers; findings were similar in non-SLE women. Two cases of congenital heart block were observed out of 100 anti-Ro/SSA positive women. In conclusion, anti-Ro/SSA antibodies are responsiblefor congenitalheart block but do not affect other pregnancyoutcomes,both in SLE and in non-SLE women. The general outcome of these pregnancies is now very good, if prospectively followedby multidisciplinaryteams with ample experiencein this field.

Anti-Mi-2 antibodies

Autoantibodies targeting the Mi-2 nuclear antigen represent one of the serologic hallmarks of idiopathic inflammatory myopathies, with a diagnostic sensitivity and specificity of approximately 4–18% and 98–100%, respectively. Mi-2 antigen is a component of the nuclesome remodeling-deacetylase (NuRD) complex involved in transcription regulation. Anti-Mi-2 antibodies are strongly associated with dermatomyositis (frequency up to 31%) and have a very high positive predictive value for such disease subset. A strong correlation with HLA-DR7 has been demonstrated. At the moment, optimal serologic testing is achieved by ELISA screening on ricombinant Mi-2 antigen and confirmation of positive results on immunoblot.

Clinical and laboratory manifestations of elderly onset psoriatic arthritis: a comparison with younger onset disease

OBJECTIVE Although the influence of age on clinical and laboratory features has been widely demonstrated in many arthropathies, studies on elderly onset (> 60 years) psoriatic arthritis (EOPsA) are rare. This study compares manifestations at onset and two year outcome of EOPsA with those of younger onset PsA (YOPsA). PATIENTS AND METHODS Sixty six consecutive PsA patients with disease duration < 1 year, 16 EOPsA (>60 years) and 50 YOPsA (⩽60 years) were admitted to a prospective study. Clinical, laboratory, and radiographic assessment were carried out at admission and after two years. HLA class I and bone scintigraphy were also recorded. In 10 patients with EOPsA and 24 with YOPsA it was possible to obtain synovial fluid, which was subsequently analysed for local inflammatory indices, including interleukin (IL) 1β, IL6, and IL8. RESULTS Presenting manifestations of EOPsA differed from YOPsA in number of active joints (mean (SD)) (12.2 (6.3) v 6.7 (4.6), p<0.001), foot bone erosions (2.7 (1.2) v1.1 (1.1), p<0.001), erythrocyte sedimentation rate (64.2 (35.3)v 30.5 (30.0) mm 1st h, p<0.001), C reactive protein (3.9 (2.0) v 1.3 (1.3) mg/dl, p<0.001) and synovial fluid IL1β (8.0 (4.7)v 3.0 (3.0) pg/ml, p<0.001) and IL6 (828.2 (492.6) v 469.3 (201.4) pg/ml, p<0.005). No differences were found in the number of subjects with dactylitis, pitting oedema, HLA-B27, or signs of sacroiliac and sternoclavicular joint involvement at bone scintigraphy. After two years, progression was more evident in EOPsA than in YOPsA, as the number of new erosions in the hands and also the C reactive protein were higher in EOPsA patients. CONCLUSION PsA has a more severe onset and a more destructive outcome in elderly people (onset >60 years) than in younger subjects. This behaviour may be influenced by immune changes associated with aging, as suggested by the higher concentrations of IL1β and IL6 found in the synovial fluid of EOPsA than in YOPsA.

Anti-ribosomal P protein antibodies detected by immunoblotting in patients with connective tissue diseases: their specificity for SLE and association with IgG anticardiolipin antibodies.

OBJECTIVE To assess the prevalence and clinical and serological associations of anti-ribosomal P protein antibodies (anti-P antibodies) in patients with connective tissue diseases (CTDs) and investigate the immunobiological nature of autoantibody clustering in which anti-P antibodies play a part. METHODS IgG anti-P antibodies in the sera of 267 patients with CTDs and 31 healthy subjects were analysed by immunoblotting performed on cytoplasmic extract of Raji cells. 60 patients with systemic lupus erythematosus (SLE), 32 systemic sclerosis, 46 primary Sjögrens syndrome, 16 poly/dermatomyositis, 11 rheumatoid arthritis, 8 undifferentiated CTD, 72 overlap CTD, and 22 primary antiphospholipid syndrome were studied. Anti-P antibodies were affinity purified by elution from nitrocellulose bound antigen and tested by ELISA for their binding activity to cardiolipin. RESULTS Anti-P antibodies were detected in 16 (6%) patients and in none of the controls: 12/60 SLE (20%) and 4/80 undifferentiated/overlap patients with CTD (5%). A close association of IgG antibodies with P proteins and with cardiolipin was seen in lupus sera (p=0.0009, odds ratio 18.33). Anti-P antibodies from 9 of 12 anti-P lupus serum samples could be affinity purified and none of the affinity purified fractions cross reacted with ELISA plate coated cardiolipin. CONCLUSIONS Anti-P immunoreactivity is a specific marker of SLE and lupus-like disease and its detection is recommended as a powerful diagnostic tool. Anti-P antibodies are strongly clustered with IgG anticardiolipin antibodies in lupus sera, even if they are independently elicited. This suggests that their cognate autoantigens play a part in a common pathogenetic pathway in SLE.

Anti-Jo-1 Antibodies

Anti-Jo-1 antibody is a myositis specific autoantibody most commonly found in patients with idiopathic inflammatory myopathies (IIM). This antibody is directed against the histidyl-tRNA synthetase which catalyses the binding of the histidine to its cognate tRNA during protein synthesis. It can be considered a specific marker of IIM, predominantly found in 20–30% of patients with PM and in the 60–70% of those with interstitial pulmonary fibrosis. These antibodies are also found in DM, although less frequently than in PM, and are rare in children with PM or DM and in other connective tissue diseases. ELISA, CIE and immunoblotting are highly specific and sensitive techniques for testing anti-Jo-1 antibodies. The detection of this antibody is particularly useful in diagnosis and classification of IIM. Moreover, anti-Jo-1 serum levels strongly correlate with disease activity representing a good marker for disease monitoring.

Antiphospholipid antibodies (aPL) in systemic lupus erythematosus. Are they specific tools for the diagnosis of aPL syndrome

OBJECTIVE--Antiphospholipid antibody (aPL) specificity for aPL-related events was evaluated in systemic lupus erythematosus (SLE). METHODS--A study was carried out on 105 patients affected with SLE comparing the prevalence of lupus anticoagulant (LA) and IgG and IgM anticardiolipin antibodies (aCL) between patients with and without features of antiphospholipid syndrome (APS). Antiphospholipid antibody profile was subsequently evaluated in the aPL positive patients with and without aPL-related events, thus excluding the patients with complications of APS possibly due to factors other than aPL. RESULTS--LA showed a strong association with thrombosis and livedo reticularis, and IgG aCL with thrombosis and neurological disorders, while no clinical features were associated with IgM aCL. A considerable number of aPL positive patients with no aPL-related manifestations was also observed, suggesting the low specificity of aPL assays (54.4%). When studying the 60 aPL positive patients, LA was specific (91.3%) for the diagnosis of aPL-related thrombosis, whereas aCL were not specific, although IgG aCL mean levels were higher in patients with arterial thrombosis than in those without APS features. CONCLUSIONS--LA but not aCL positivity is a specific tool for the diagnosis of thrombotic complications due to aPL in SLE.

Gynaecological aspects of primary Sjogren's syndrome

UNLABELLED Female patients affected with Sjogrens Syndrome (SS) frequently describe symptoms such as vaginal dryness and dyspareunia; however, only a few controlled studies have regarded clinical involvement of the female external genitalia. OBJECTIVE The present study was undertaken in order to: (1) Evaluate the involvement of external genitalia in a large number of female patients affected with primary SS (pSS) by semi-quantitative methods covering subjective symptoms and clinical evaluation. (2) Compare pSS patients with a matched healthy control group (pre- and post-menopausal women were separately studied). (3) Correlate the gynaecological involvement with salivary and lacrimal abnormalities in pSS patients. METHODS We evaluated 36 patients with primary SS (18 pre- and 18 post-menopausal women) and 43 healthy controls using a questionnaire regarding vulvar and vaginal dryness and a complete gynaecological examination. Subsequently, three scores related to vulvar and cervical status plus a global score were obtained. In primary SS patients, salivary and lacrimal involvement was also evaluated. RESULTS Dyspareunia was present in 61% and vaginal dryness in 55% of SS patients versus 39% and 33% of healthy controls. No significant differences regarding gynaecological scores were found between SS patients and controls, in both pre- and post-menopausal women, nor correlation was observed between gynaecological and lacrimal or salivary involvement. CONCLUSIONS Our data suggest that although SS patients frequently complain of dyspareunia and vaginal dryness they do not greatly differ from healthy subjects in regard to some major gynaecological aspects.

Value of synovial fluid interleukin-1 beta determination in predicting the outcome of psoriatic monoarthritis.

OBJECTIVE: To investigate the value of synovial fluid analysis in predicting the outcome of psoriatic monoarthritis. METHODS: In synovial fluid from knee joints of 18 patients with psoriatic monoarthritis lasting less than six months, white blood cell count, acid phosphatase, lysozyme, and interleukin (IL)-1 beta were determined. ESR and serum C reactive protein were also measured. To define the outcome, the patients were monitored for at least three years and then subdivided into those with polyarthritis and those without. RESULTS: Among the blood and synovial fluid indices considered, synovial fluid IL-1 beta was the only variable which differed between the patients who developed polyarthritis, within three years and those without polyarthritis after this time, at 20.82(SD 8.79) v 4.19(4.73) pg ml-1, P < 0.0001). A correlation was found between synovial fluid IL-1 beta concentrations and the number of affected joints after three years (r = 0.739, P < 0.0001). CONCLUSIONS: Determination of synovial fluid IL-1 beta at disease onset may be useful in revealing the outcome of psoriatic monoarthritis since, among the variables considered in our study, this was the only one capable of predicting the evolution of monoarticular psoriatic arthritis to polyarthritis.