Screening for latent tuberculosis infection: performance of tuberculin skin test and interferon-γ release assays under real-life conditions.

OBJECTIVES: To characterise optimal screening strategies for latent tuberculosis infection (LTBI) prior to the initiation of anti-tumour necrosis factor therapy. METHODS: Patients in 62 German rheumatology centres were evaluated for LTBI. Each patient was screened with a tuberculin skin test (TST) and one form of an interferon-γ release assay (IGRA), either TSPOT.TB (TSPOT) or Quantiferon TB Gold (QFT). RESULTS: A total of 1529 patients with rheumatological disease were tested with a TST, 844 with TSPOT and 685 with QFT. TST was positive in 11.3% (n=173). The prevalence of LTBI was 8.0% when defined as a positive TST and no previous Bacille Calmette-Guérin (BCG) vaccination and 7.9% when based on a positive IGRA. Combining both estimates increased the prevalence of LTBI to 11.1%. Clinical risk factors for LTBI were found in 122 patients (34 with a history of prior TB, 81 close contacts and 27 with suggestive chest x-ray lesions). A compound risk factor (CRF) was defined as the presence of at least one of these three risk factors. Statistical analyses were conducted to examine the association between CRF and LTBI test outcomes. In multivariate analysis, TST was influenced by CRF (OR 6.2; CI 4.08 to 9.44, p<0.001) and BCG vaccination status (OR 2.9; CI 2.00 to 4.35, p<0.001). QFT and TSPOT were only influenced by CRF (QFT: OR 2.6; CI 1.15 to 5.98, p=0.021; TSPOT: OR 8.7; CI 4.83 to 15.82, p<0.001). ORs and the agreement of TST and IGRA test results varied by rheumatological disease. CONCLUSION: LTBI test results in an individual patient need to be considered in the context of prior BCG vaccination and clinical risk factors. In patient populations with low rates of TB incidence and BCG vaccination, the use of both TST and IGRA may maximise sensitivity in detecting LTBI but may also reduce specificity.

Efficacy of sulfasalazine in patients with inflammatory back pain due to undifferentiated spondyloarthritis and early ankylosing spondylitis: a multicentre randomised controlled trial.

OBJECTIVES: To assess the effect of sulfasalazine (SSZ) on inflammatory back pain (IBP) due to active undifferentiated spondyloarthritis (uSpA) or ankylosing spondylitis in patients with symptom duration <5 years. METHODS: Patients with IBP and a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) >3 from 12 centres were randomly assigned to 24 weeks' treatment with SSZ 2 g/day or placebo. The primary outcome variable was the change in BASDAI over 6 months. Secondary outcomes included measures of spinal pain, physical function and inflammation. RESULTS: 230 patients (50% men, age range 18-64 years, 67% human leucocyte antigen B27 positive) were treated with either SSZ 2x1 g/day or placebo for 6 months. Enthesitis was found in 50%, and peripheral arthritis in 47% of the patients. The mean (SD) BASDAI dropped markedly in both groups: by 3.7 (2.7) and 3.8 (2.4), respectively, as did most secondary outcome measures. No noticeable difference in treatment was observed between groups. Patients with IBP and no peripheral arthritis had significantly (p = 0.03) more benefit with SSZ (BASDAI 5.1 (1.3) to 2.8 (2.3)) than with placebo (5.2 (1.6) to 3.8 (2.4)). Spinal pain (p = 0.03) and morning stiffness (p = 0.05) improved with SSZ in these patients, but other secondary outcomes were not markedly different. CONCLUSION: SSZ was no better than placebo for the treatment of the signs and symptoms of uSpA; however, SSZ was more effective than placebo in the subgroup of patients with IBP and no peripheral arthritis.

Development of a solid phase enzyme immunoassay for the detection of anti-Ro autoantibodies.

An enzyme immunoassay was developed to detect anti-Ro(SS-A) autoantibodies. Both Ro-antigen components (52 and 60 kD) were purified from a pig spleen extract, using fast protein liquid chromatography (FPLC). Anti-La, anti-RNP, anti-DNA and anti-Sm antibodies do not react to the purified antigen. There was a strong correlation between anti-Ro activity in EIA and the titers in counter immunoelectrophoresis (rs = 0.893). Anti-Ro antibodies were found in 54 (69.2%) of 78 SLE sera by the developed EIA.

[Detection of autoantibodies to extractable nuclear antigens in autoimmune diseases of rheumatic origin using immunoblotting--comparison with counter-electrophoresis]. / Nachweis von Autoantikörpern gegen extrahierbare nukleäre Antigene (ENA) bei Autoimmunerkrankungen des rheumatischen Formenkreises mittels Immunoblotting--Vergleich mit der Gegenstromelektrophorese.

Sera from 82 patients with rheumatic autoimmune disease were tested for anti-ENA antibodies by immunoblotting and counterimmunoelectrophoresis (CIE), using HeLa cell extract and rabbit thymus extract, respectively, as antigens. Anti-ENA antibodies were more frequently detected and could be better differentiated by immunoblotting rather than by CIE. There was especially an increase in anti-Sm antibodies (23, in contrast to four positive results), which was only detectable in serum samples for the 59 SLE patients. The sera of the six patients with MCTD all reacted with the 68 U1-RNP antigen. The sera of the five patients with Sjögren's syndrome only recognized the 50k La antigen, while other anti-ENA antibodies were not observed. In SLE anti-La antibodies were often associated with other anti-ENA antibodies. Seven out of eight SLE patients showing a combined detection of antibodies against Sm, U1-RNP and La by immunoblotting demonstrated severe organ involvements, especially lupus nephritis. Therefore, the characterization of anti-ENA antibodies by immunoblotting may contribute to improve the differentiation of connective tissue diseases.

Development of a DNA-adsorbent for the specific removal of anti-DNA autoantibodies in systemic lupus erythematosus (SLE).

Autoantibodies against DNA are of primary importance for the diagnosis and pathogenesis of systemic lupus erythematousus (SLE). The level of anti-DNA antibodies correlates well with the disease activity and renal involvement. In such patients the removal of anti-DNA antibodies from plasma may lead to a clinical improvement. For this reason an adsorbent was made by covalent coupling of calf thymus DNA to a solid support based on ethylene dimethacrylate cross-linked hydroxethyl methacrylate. Up to 2.5 mg of DNA were immobolized to 1 ml of the support activated chemically by aminosilane and glutaraldehyde. The incubation of 40 ml of SLE plasma with 1 ml of the adsorbent resulted in a 50% decline in anti-DNA activity. There was no release of immobilized P-32-DNA into the plasma. Biocompatibility, sterilisation, and reapplication (without loss of binding capacity) of the adsorbent could be demonstrated. We concluded that the adsorbent may be suitable for treatment.

[Fibronectin concentrations in the plasma of newborn infants and their mothers and various plasma preparations]. / Fibronektinkonzentrationen im Plasma von Neugeborenen und deren Müttern sowie verschiedenen Plasmaprärationen.

The article describes a method for the quantification of plasma fibronectin (FN) by means of electroimmunodiffusion after Laurell. By this means the fibronectin concentrations of healthy, mature newborns as well as of their mothers were determined. The average FN-level of the newborns lies at 33% related to the value for adults and at 48%, respectively, related to the maternal FN-content. There is no difference between male and female newborns. The FN-concentrations of the adults stated by us with 330 and 314 mg/l, respectively, for males and females correspond to the data in literature. Furthermore, the FN-content in plasma preparations was determined, with an average value of 2,356 mg/l this was highest in the factor-VIII-concentrate. The expediency and the prerequisites for a possible fibronectin substitution are discussed.

[Plasma fibronectin in acute leukemia. Effects of the cytostatic therapy on plasma fibronectin level]. / Plasma-Fibronectin bei akuter Leukämie. Der Einfluss der zytostatischen Therapie auf den Plasma-Fibronectinspiegel.

Twice a week plasma (Pl.)-fibronectin was determined quantitatively in the course of disease with immunoelectrophoresis according to Laurell in 12 patients suffered from acute non-lymphoblastic leukemia (ANLL) and in 12 patients affected with acute lymphoblastic leukemia (ALL). At diagnosis Pl.-fibronectin concentration was found to be significantly lowered only in those patients affected with ANLL. During the induction therapy Pl.-Fibronectin could be observed to decline significantly in all patients: in acute non-lymphoblastic leukemia from mean 270 micrograms/ml, s 93 micrograms/ml, to mean 185 micrograms/ml, s 89 micrograms/ml (p less than 0.01), and in acute lymphoblastic leukemia from mean 290 micrograms/ml, s 98 micrograms/ml, to mean 180 micrograms/ml, s 94 micrograms/ml (p less than 0.01). After administering L-asparaginase there is a strong decline of Pl.-fibronectin. Pl.-fibronectin concentration could be observed to be significantly lower in patients without remission in comparison to those with remission. A correlation between Pl.-fibronectin concentration and tumour mass could not be identified.

[The role of fibronectin in nonspecific defense from the immunologic viewpoint]. / Zur Rolle von Fibronektin bei der unspezifischen Abwehr aus immunologischer Sicht.

The present article gives a review of the essential data of literature concerning the importance of fibronectin (Fn) for the unspecific defence. In this case the function of Fn postulated as unspecific opsonin stands in the foreground. Fn mediates the binding of gelatine particles, bacteria and other above all particular materials on phagocytizing cells (monocytes, macrophages and neutrophils). Up to now it is, however, controversial whether or not this binding causes an increased endocytosis. The participation of cofactors or inhibitors and the problem whether Fn or certain proteolytic Fn-fragments are effective still need a further clarification. Fn, its fragments or Fn-substrate-complexes can activate phagocytes and have a chemotactic effect on them. The mechanism of activation is still unknown, for monocytes in increased expression of Fc- and C3b-receptors is supposed. Fn might consequently perform a defence function as an unspecific cell activator and at the same time have a pro-inflammatory influence. There are controversial opinions as to the questions which phagocytes are activated and which Fn-molecules (complete plasma-Fn or fragments) are responsible. The high sensitiveness of Fn to proteolytic enzymes and denaturating processes is supposed to be one of the causes for the different results.

A simple and fast method for the preparation of the human cardiac myosin light chains.

A simple and fast method is presented for the isolation and separation of human cardiac myosin light chains. The method requires only a crude myosin for splitting into heavy and light chains. The separation of the light chains is made by isoelectric precipitation with good yield.

[Digestive and endocrine functions after partial duodeno-pancreatectomy]. / Digestive und inkretorische Funktionen nach partieller Duodeno-Pankreatektomie

Pancreatico-duodenectomy was performed in 11 patients for malignant or inflammatory tumours of the head of the pancreas or the region of the papilla. Digestive and endocrine functions were determined after the operation. In all cases faecal fat values were abnormal, indicating a 90% loss of pancreas. 14C-exhalation measurement, chymotrypsin determination in stool, and amylose tolerance test were also performed. Oral glucose-tolerance tests with plasma-insulin measurement indicated asymptomatic diabetes mellitus in the majority of patients. Two patients whose diabetes was controlled by tablets before the operation required insulin treatment afterwards. A decreased serum-gastrin level proved the existence of gastric and extragastric sources of gastrin.