Predicting development of sustained unresponsiveness to milk oral immunotherapy using epitope-specific antibody binding profiles

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Diagnostic performance of aPS/PT antibodies in neuropsychiatric lupus and cardiovascular complications of systemic lupus erythematosus

Abstract

Background: Systemic lupus erythematosus (SLE) is associated with a constellation of complications affecting multiple organs, including neuropsychiatric manifestations (NPSLE) and ischaemic events, leading to increased long-term morbidity. Antiphospholipid antibodies (aPL) are a major determinant of vascular inflammation and thromboembolic risk. The diagnostic role of anti-phosphatidylserine/prothrombin (aPS/PT) antibodies in this setting is incompletely defined.

Aim: To verify whether aPS/PT add to diagnostics and disease stratification in patients with SLE with or without other aPL.

Methods: 131 consecutive patients were studied, including 20 patients with SLE and secondary antiphospholipid syndrome (APS). aPS/PT IgG and IgM were assessed through ELISA and patients were stratified based on the presence of other aPL, on their clinical and laboratory features at time of blood sampling and on their clinical history. Synthetic indices of disease activity, chronic damage and cardiovascular risk were calculated at time of venipuncture.

Results: Fifty-one (38.9%) patients with SLE had aPS/PT and 15 (11.5%) patients had aPS/PT as the only aPL (aPS/PT-only). aPS/PT-only patients had a significantly higher prevalence of NPSLE than quadruple aPL-negative patients (p?=?.007). Patients with aPS/PT were more likely to have a history of ischaemia, thrombocytopenia and Libman–Sacks’ endocarditis. The presence of aPS/PT also associated with previous accrual of at least one damage item (p?=?.043), but had limited predictive values for damage progression in the short term.

Conclusion: aPS/PT antibodies provide non-redundant information that could contribute to risk assessment and stratification of patients with SLE.     

Prevalences, genotypes, and risk factors for HIV transmission in South America

HIV cross-sectional studies were conducted among high-risk populations in 9 countries of South America. Enzyme-linked immunosorbent assay screening and Western blot confirmatory testing were performed, and env heteroduplex mobility assay genotyping and DNA sequencing were performed on a subset of HIV-positive subjects. HIV prevalences were highest among men who have sex with men (MSM; 2.0%-27.8%) and were found to be associated with multiple partners, noninjection drug use (non-IDU), and sexually transmitted infections (STIs). By comparison, much lower prevalences were noted among female commercial sex workers (FCSWs; 0%-6.3%) and were associated mainly with a prior IDU and STI history. Env subtype B predominated among MSM throughout the region (more than 90% of strains), whereas env subtype F predominated among FCSWs in Argentina and male commercial sex workers in Uruguay (more than 50% of strains). A renewed effort in controlling STIs, especially among MSM groups, could significantly lessen the impact of the HIV epidemic in South America.     

Characterization of the major secreted zinc metalloprotease- dependent glycerophospholipid:cholesterol acyltransferase, PlaC, of Legionella pneumophila

Legionella pneumophila, an intracellular pathogen causing a severe pneumonia, possesses distinct lipolytic activities which have not been completely assigned to specific enzymes so far. We cloned and characterized a gene, plaC, encoding a protein with high homology to PlaA, the major secreted lysophospholipase A of L. pneumophila and to other hydrolytic enzymes belonging to the GDSL family. Here we show that L. pneumophila plaC mutants possessed reduced phospholipase A and lysophospholipase A activities and lacked glycerophospholipid:cholesterol acyltransferase activity in their culture supernatants. The mutants' reduced phospholipase A and acyltransferase activities were complemented by reintroduction of an intact copy of plaC. Additionally, plaC conferred increased lysophospholipase A and glycerophospholipid:cholesterol acytransferase activities to recombinant Escherichia coli. Furthermore, PlaC was shown to be another candidate exported by the L. pneumophila type II secretion system and was activated by a factor present in the bacterial culture supernatant dependent on the zinc metalloprotease. Finally, the role of plaC in intracellular infection of Acanthamoeba castellanii and U937 macrophages with L. pneumophila was assessed, and plaC was found to be dispensable. Thus, L. pneumophila possesses another secreted lipolytic enzyme, a protein with acyltransferase, phospholipase A, and lysophospholipase A activities. This enzyme is distinguished from the previously characterized phospholipases A and lysophospholipases A by its capacity not only to cleave fatty acids from lipids but to transfer them to cholesterol. Cholesterol is an important compound of eukaryotic membranes, and an acyltransferase might be a tool for host cell modification to fit the needs of the bacterium.     

Inhibition of Chlamydia pneumoniae replication in human aortic smooth muscle cells by gamma interferon-induced indoleamine 2, 3-dioxygenase activity

Infection with Chlamydia pneumoniae, a human respiratory pathogen, has been implicated as a potential risk factor in atherosclerosis, possibly because the pathogen can exist in a persistent form similar to that described for Chlamydia trachomatis. The present study investigated whether gamma interferon (IFN-gamma) can induce indoleamine 2,3-dioxygenase (IDO) activity in aortic smooth muscle cells, leading to a marked inhibition of C. pneumoniae growth. Our data indicate a stimulation of IDO mRNA expression and dose-dependent enzymatic activity following IFN-gamma treatment. IDO-mediated increase in tryptophan catabolism resulted in a dose-dependent marked inhibition of C. pneumoniae replication.     

Comparison of different extraction methods of Alternaria allergens

Spore and mycelial allergens of two species of Alternaria (A. brassicicola and A. alternata) extracted under two different conditions were analyzed by radiorocket immunoelectrophoresis, crossed radioimmunoelectrophoresis, and Western blotting with a pool of sera from Alternaria-allergic patients. More allergens were extracted after disruption of the cells if protease inhibitors and a phenol-binding component were included in the homogenization buffer. However, the 31 kDa major allergen was extracted in about the same amount, either by incubation or by cell breakage of the cells. This 31 kDa allergen was present in higher concentration in the mycelium than in the spore. The difference between the two species studied is less than between spore and mycelium from the same species.     

Disturbance of motor imagery after cerebellar stroke

The authors studied the possible involvement of the cerebellum in nonexecutive motor functions needed for a normal performance of complex motor patterns by analyzing (using chronometric evaluation) finger movement sequences and their respective motor imagery (a mental simulation of motor patterns). Patients suffering from a cerebellar stroke (n=11) were compared with aged-matched control volunteers (n=11). Patients that had apparently recovered from a unilateral cerebellar stroke showed a marked slowing of motor performance in both hands (ipsi- and contralateral to lesion). This effect was accompanied by a similar slowing of motor imagery, suggesting that the cerebellum, traditionally implicated in the control of motor execution, is also involved in nonexecutive motor functions such as the planning and internal simulation of movements.     

First case of compound heterozygous BHLHA9 variants in mesoaxial synostotic syndactyly with phalangeal reduction

Mesoaxial synostotic syndactyly with phalangeal reduction (MSSD) is an extremely rare autosomal recessive limb abnormality characterized by the fusion of third and fourth fingers. To date, only homozygous missense and frameshift mutations have been reported in BHLHA9 associated to MSSD. In this study, we report a patient who presented with clinical and radiological features of MSSD. A customized skeletal dysplasia NGS panel revealed the presence of two novel compounds heterozygous variants in BHLHA9: NM_001164405.1: c.[226A>T][269G>C]; p.[(Lys76*)][(Arg90Pro)]. Thus, this is the first case of MSSD in a nonconsanguineous family.     

Patient with multiple congenital anomalies and decreased production and processing of procollagen in cultured fibroblasts

We report on a patient with hip and elbow dislocations, joint hyperextensibility, peculiar facial appearance, torticollis, cryptorchidism, unilateral hexadactyly, and other minor anomalies. Cultured cells from this patient produce less type I procollagen and have a slower rate of processing of type I procollagen to collagen in the culture medium. We think that the pattern of clinical anomalies constitutes a previously unreported syndrome with type I procollagen defect as a manifestation of the syndrome.