Smoking,disease activity,permanent damage and dsDNA autoantibody production in patients with systemic lupus erythematosus

The aim was to study the association of smoking with the activity and severity of systemic lupus erythematosus (SLE) and the production of antibodies to dsDNA. The study included 223 SLE patients attending the outpatient clinics at Helsinki University Central Hospital. The history of smoking was obtained by personal interview, and clinical data related to SLE by interview, clinical examination and chart review. The activity of SLE was assessed by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score and permanent damage by the SLICC/ACR score. Antibodies to dsDNA were determined by three ELISA assays, by the indirect immunofluorescence technique using Crithidia luciliae cells as substrates and by the Farr assay. There were no significant differences in the SLEDAI scores between current smokers (73 patients), ex-smokers (59) and never-smokers (91), though current smokers tended to have lower disease activity. The SLICC/ACR scores between the groups were practically equal. Current smokers had significantly lower levels of antibodies to dsDNA than ex- and never-smokers (p = 0.025). Our study suggests that cigarette smoke may have immunosuppressive effect on autoantibody production in patients with SLE. Permanent damage was not found to be associated with smoking.     

Neuromyelitis optica and aquaporin‐4 (AQP4) autoantibodies in consecutive optic neuritis patients in Southern Finland

Purpose: To analyse the frequency of neuromyelitis optica (NMO) among consecutive optic neuritis (ON) patients in Southern Finland and the feasibility of Aquaporin‐4 (AQP4) autoantibody assay in the diagnosis of NMO. Methods: Consecutive patients with symptoms suggestive of acute ON and managed in the Helsinki University Central Hospital were evaluated critically screened for AQP4 autoantibody during a 47.5‐month period. The antibodies were determined using radioimmunoprecipitation method. AQP4 index >15 was considered positive, 10–15 borderline and <10 normal. Brain magnetic resonance imaging (MRI) was performed for all patients. Results: Of the 300 patients with suspected ON, 191 were eventually diagnosed as ON, and 66 (35%) of them had a previous diagnosis or were diagnosed with multiple sclerosis (MS). Of the 125 patients without MS diagnosis, 62 (50%) had demyelinative lesions in MRI, which is a risk factor for developing MS. Two patients (1.1%; 95% CI 0.3–4.5) fulfilled the criteria of NMO. Positive AQP4 antibodies were found in three patients (1.6% 95% CI 0.3–4.5), one of them had NMO, one had MS and one became diagnosed with MS a month later. Borderline autoantibody levels were found in 10 patients, 7 of whom had MS. Conclusions: NMO is rare among ON patients in the population of Southern Finland. In this small cohort, the sensitivity and positive predictive values of the AQP4 autoantibody index for NMO were low, 1/2 and 1/3 respectively, and do not support initiating routine screening.     

Management of Habitual Abortion

Examination of the habitual aborter should include, in addition to routine studies, a hysterogram, determination of basal metabolic rate, body temperature charting, and endometrial biopsy. Study of the husband is also recommended. Preconceptional management is aimed at improving health and nutrition, eliminating gynecologic abnormalities, and supporting an inadequate secretory endometrium. When pregnancy occurs, management calls for adequate rest, good nutrition, administration of progestogens, and frequent examination.     

Treatment of restless legs syndrome: Evidence‐based review and implications for clinical practice (Revised 2017)§

The objective of the current review was to update the previous evidence‐based medicine review of treatments for restless legs syndrome published in 2008. All randomized, controlled trials (level I) with a high quality score published between January 2007 and January 2017 were reviewed. Forty new studies qualified for efficacy review. Pregabalin, gabapentin enacarbil, and oxycodone/naloxone, which did not appear in the previous review, have accrued data to be considered efficacious. Likewise, new data enable the modification of the level of efficacy for rotigotine from likely efficacious to efficacious. Intravenous ferric carboxymaltose and pneumatic compression devices are considered likely efficacious in idiopathic restless legs syndrome. Bupropion and clonidine were reviewed, but the lack of data determined a rating of insufficient evidence for efficacy. The following interventions continue to be considered efficacious as in 2008: levodopa, ropinirole, pramipexole, cabergoline, pergolide, and gabapentin. Bromocriptine, oxycodone, carbamazepine, and valproic acid are considered likely efficacious. Oral iron is nonefficacious in iron‐sufficient subjects, but its benefit for patients with low peripheral iron status has not been adequately evaluated. Restless legs syndrome augmentation has been identified as a significant long‐term treatment complication for pramipexole more than pregabalin and possibly for all dopaminergic agents more than α2δ ligands. Therefore, special monitoring for augmentation is required for all dopaminergic medications as well as tramadol. Other drugs also require special safety monitoring: cabergoline, pergolide, oxycodone, methadone, tramadol, carbamazepine, and valproic acid. Finally, we also highlighted gaps and needs for future clinical research and studies of restless legs syndrome. © 2018 International Parkinson and Movement Disorder Society     

Aire deficient mice do not develop the same profile of tissue-specific autoantibodies as APECED patients

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED, or APS1), is a monogenic autoimmune disease caused by mutations in the autoimmune regulator (AIRE) gene. The three main components of APECED are chronic mucocuteaneous candidiasis, hypoparathyroidism and adrenocortical insufficiency. However, several additional endocrine or other autoimmune disease components, or ectodermal dystrophies form the individually variable clinical picture of APECED. An important feature of APECED is a spectrum of well-characterized circulating autoantibodies, reacting against tissue-specific autoantigens. Aire deficient mice develop some characteristics of APECED phenotype. In order to investigate whether the Aire deficient mice produce autoantibodies similar to human APECED, we studied the reactivity of Aire mouse sera against mouse homologues of 11 human APECED antigens. None of the APECED antigens indicated elevated reactivity in the Aire knock-out mouse sera, implying the absence of APECED associated autoantibodies in Aire deficient mice. These findings were supported by the failure of the autoantigens to activate mouse T-cells. Furthermore, Aire knock-out mice did not express increased levels of anti-nuclear antibodies compared to wt mice. This study indicates that spontaneous induction of tissue-specific autoantibodies similar to APECED does not occur in the rodent model suggesting differences in the immunopathogenic mechanisms between mice and men.     

Nonrenal and renal activity of systemic lupus erythematosus: a comparison of two anti-C1q and five anti-dsDNA assays and complement C3 and C4

Associations of different assays for antibodies to C1q (anti-C1q) and to dsDNA (anti-dsDNA) and of complements C3 and C4 with disease activity in patients with systemic lupus erythematosus (SLE) were studied. The clinical manifestations of 223 SLE patients were recorded, and the disease activity was assessed by the SLEDAI score. Anti-C1q were determined by two enzyme-linked immunosorbent assays (ELISA) and anti-dsDNA by a radioimmunoassay (RIA), a Crithidia immunofluorescence (IF) assay and three ELISA assays using human telomere DNA, plasmid DNA circles, or calf thymus DNA as antigens, respectively. Complement C3 and C4 were determined by nephelometry. Control sera were obtained from 98 blood donors. In patients with SLE, the prevalence of anti-C1q was 17–18% and that of anti-dsDNA was 36–69%. Anti-C1q, anti-dsDNA, and complement C3 and C4 correlated well with the overall activity of SLE (r?=?0.323–0.351, 0.353–0.566, and ?0.372–0.444, respectively; P?<?0.001). Sensitivity, specificity, positive predictive value, and negative predictive value for active lupus nephritis among SLE patients were 40–44, 92, 29, and 91–92% for anti-C1q and 48–68, 29–66, 11–16, and 86–91% for anti-dsDNA, respectively. Patients with active nephritis had higher levels of anti-C1q and lower levels of C3 and C4 than patients with inactive nephritis (P?=?0.003–0.018). The corresponding associations of anti-dsDNA were somewhat weaker (P?=?0.023–0.198). Hematological parameters reflecting disease activity correlated clearly better with anti-dsDNA and complement C3 and C4 than with anti-C1q. Anti-C1q is inferior to anti-dsDNA as a diagnostic test in SLE and in the evaluation of overall clinical activity of the disease. Anti-C1q together with complement C3 and C4 may offer useful additional information to monitor lupus nephritis activity. There are no practical differences between different assays for anti-C1q and anti-dsDNA.     

Extracellular prolyl oligopeptidase derived from activated microglia is a potential neuroprotection target

Prolyl oligopeptidase (PREP) is an abundant peptidase in the brain and periphery, but its physiological functions are still largely unknown. Recent findings point to a role for PREP in inflammatory processes. This study assessed the cellular and extracellular PREP activities in cultures of mouse primary cortical neurons, microglial cells and astrocytes, and immortalized microglial BV‐2 cells under neuroinflammatory conditions induced by lipopolysaccharide (LPS) and interferon gamma (IFNγ). Furthermore, we evaluated the neuroprotective effect of a specific PREP inhibitor, KYP‐2047, in a neuroinflammation model based on a coculture of primary cortical neurons and activated BV‐2 cells. The inflammatory insult reduced intracellular and increased extracellular PREP activity specifically in microglial cells, suggesting that activated microglia excretes active PREP. A targeted proteomics approach revealed up‐regulation in PREP protein levels in BV‐2 cell growth medium but down‐regulation in crude membrane‐bound PREP after LPS+IFNγ. In the coculture of BV‐2 cells and primary neurons, an increase in extracellular PREP activity was also detected after inflammation. KYP‐2047 (10 μmol/L) significantly protected neurons against microglial toxicity and reduced the levels of the pro‐inflammatory cytokine tumour necrosis factor alpha. In conclusion, these data point to an extracellular role for microglial PREP in the inflammatory process. Inhibition of PREP during neuroinflammation is a potential target for neuroprotection. Thus, PREP inhibitors may offer a novel therapeutic approach for the treatment of neurodegenerative disorders with an inflammatory component including Parkinson's and Alzheimer's diseases.     

Teratologic Congenital Dislocation of the Hip: Report of Two Cases

The incidence of teratologic dislocation of the hip is about 0.04 per thousand. Teratologic CDH is usually described together with other anomalies, such as arthrogryposis.

Quite different opinions about the diagnostic criteria are found in the literature; some of these are reviewed in this report. Two cases of teratologic CDH with no other anomalies are also reported.

Computer tomography was used to confirm reduction in plaster when conventional radiologic examination gave ambiguous results.