Association between human leukocyte antigen-DR and demylinating Guillain-Barré syndrome

Objective:

To find an association between human leukocyte antigen (HLA) class II DRB1, DRB3, DRB4, and DRB5 alleles frequencies in a sample of Iraqi patients with Guillain-Barré syndrome (GBS) and compare with a healthy control group.

Methods:

We performed a cross-sectional study consisting of 30 Iraqi Arab patients with GBS attending the Neurological Department in the Neuroscience Hospital, Baghdad, Iraq between September 2012 and June 2013. The control group comprised 42 apparently healthy volunteers. Human leukocyte antigen genotyping for HLA DRB1, DRB3, DRB4, and DRB5 was performed using the polymerase chain reaction-sequence-specific primers method. The allele frequencies were compared across both groups. Major histocompatibility complex (MHC)-class II HLA-DR genotyping and serotyping were performed by software analysis.

Results:

We found increased frequencies of HLA genotype DRB1*03:01 (p=0.0009), DRB1*07:01 (p=0.0015), and DRB4*01:01 (p<0.0001) in patients with GBS compared with healthy controls. The HLA DR6 was increased in the control group (p<0.0001).

Conclusions:

Our results suggest an association between HLA-DRB1*03:01, DRB1*07:01, DRB4*01:01, and HLA DR3, DR7 and a susceptibility to GBS.Guillain-Barré syndrome (GBS) is an acute inflammatory polyradiculoneuropathy that is autoimmune in nature, and manifests as a rapidly evolving reflexic motor paralysis with or without sensory disturbance and autonomic system involvement.1 Guillain-Barré syndrome is subdivided into the most common type, which is the acute inflammatory demyelinating polyneuropathy (AIDP), and an axonal variant, which is subdivided into 2 subtypes: acute motor axonal neuropathy (AMAN), and an acute motor sensory axonal neuropathy (AMSAN).2-4 There is an additional rare third type, which is Miller Fischer syndrome that accounts for only 5% of cases. The GBS prevalence is between 0.6-4/100.000 /year,5 with age range from 2 months to 95 years.6 Most patients are between 15-50 years.7,8 The autoimmune nature of the disease is triggered by a nonself-antigen (infectious agent, vaccine) that attacks gangliosides in the axonal membrane by a molecular mimicry mechanism in axonal GBS, but in AIDP, the specific antigen or antibodies are still uncertain.8,9 There is evidence that both cellular and humeral mediated immunity participates in the immune mechanism. The most common infectious agents that participate in the molecular mimicry autoimmune response are Campylobacter jejuni,10,11 cytomegalovirus,12 Epstein barr virus,13 and Mycoplasma pneumoniae.14Much of the research has focused on finding the high risk predisposition of certain people with an infection to develop GBS evidenced by a twin study, linkage disease, genetic, familial, and HLA study.15,16 The HLA antigen system is the name of the loci of genes that encode for the major histocompatibility complex (MHC) in humans. These genes reside on chromosome 6, and encode cell-surface antigen-presenting proteins, along with many other functions. The HLAs corresponding to MHC class I (A, B, and C) present peptides from inside, while HLAs corresponding to MHC class II (DP, DM, DOA, DOB, DQ, and DR) present antigens from outside of the cell to T-lymphocytes. The HLAs corresponding to MHC class III encode components of the complement system.17 In GBS, there is macrophage activation with circulating activated T-lymphocytes evidenced by augmented expression of histocompatibility antigens (HLA-DR), suggesting that there is an association between GBS and HLA alleles.15,16 The HLA typing in GBS was investigated in several studies worldwide suggesting various associations.15,16,18 The aim of the current study is to investigate any association between GBS and HLA-DR.     

Serum Prolactin Levels in Psoriasis and its Association with Disease Activity: A Case-Control Study

Background:Psoriasis is a T-cell-mediated autoimmune chronic skin disorder in which an environmental factor, perhaps a viral antigen, induces T cells to produce cytokines. These cytokines stimulate keratinocyte proliferation and production of antigenic adhesion molecules in the dermal blood vessels. Several mediators and hormones have been implicated in keratinocyte hyperproliferation and among these hormones, prolactin (PRL) has been found to have an effect on epithelial cells, lymphocytes and keratinocytes, thus an effect on the etiopathogenesis of psoriasis.Aim:The present study was designed to compare serum PRL levels in psoriatic patients with a control group.Results:Serum PRL levels were significantly increased in patients as compared to the control group (P value: 0.002). There was a positive correlation between pretreatment serum PRL levels and PASI score (r value: 0.379; P value: 0.003). An insignificant association was found between the pretreatment PRL level and serum PRL level after treatment (P value: 0.22). Also, a negative correlation between the duration of psoriasis and serum PRL was seen (r value: -0.008; P value: 0.954).Conclusion:PRL may have a role to play in the etiopathogenesis of psoriasis. However, further studies with large sample size should be carried out so as to validate this hypothesis.     

A novel biallelic variant in the Popeye domain-containing protein 1 (POPDC1) underlies limb girdle muscle dystrophy type 25

POPDC1 also known as BVES, is a highly conserved transmembrane protein, important for striated muscle function and homeostasis. Pathogenic variants in the POPDC1 gene are associated with limb-girdle muscular dystrophy type 25 (LGMDR25). In the present study, we performed trio-whole exome sequencing (WES) followed by Sanger sequencing on a single family having LGMD clinical features. Protein modeling of all POPDC1 missense variants (POPDC1^Pro134Leu, POPDC1^Ile193Ser, and POPDC1^Ser201Phe) associated with LGMDR25 were performed using Molecular Dynamics (MD) simulation. We identified a homozygous missense variant (c.401C>T; p.Pro134Leu) in the POPDC1 gene. Altered 3D structure, disruptive fluctuation, less compactness, and instability were observed in all the three variants of POPDC1 protein models. In comparison, POPDC1^Ser201Phe protein dynamics were more unstable than other variants. Functional study of newly identified variant would add key answers to underlying mechanisms of the disease.     

Enhancement of nutraceutical and anti-diabetic potential of fenugreek (Trigonella foenum-graecum). Sprouts with natural elicitors

Trigonella foenum-graecum has been extensively used for centuries in traditional medicine systems for the cure of health ailments including diabetes. Improving the medicinal attributes of plants through the elicitation strategy is gaining great interest in the recent past. In the current study, an attempt is made to reveal the role and possible mechanism of action of vitamin C elicit phytochemical-rich aqueous extract of 4th day germinated IM6 genotype fenugreek sprouts in the form of lyophilized powder (IM6E) under both in vitro and in vivo conditions. The IM6E demonstrated strong α-glucosidase activity (95.24 %) and moderate α-amylase and invertase inhibition activities under in vitro conditions. The High Performance Thin Layer Chromatography (HPTLC) based analysis demonstrated that IM6E possess significantly higher concentration of phenolic phytochemical quercetin (0.148 %) as compared to diosgenin and trigonelline bioactive anti-diabetic nutraceuticals. In normal rats after loading with glucose and sucrose, the IM6E administration in a dose-dependent manner significantly reduced the post-prandial hyperglycemia, in a similar fashion as the anti-diabetic drug voglibose as evident from the area under curves (AUC) of oral glucose tolerance test (OGTT) and oral sucrose tolerance test (OSTT) tests. The administration of IM6E in streptozotocin (STZ) induced diabetic rats drastically improved the antioxidant activity of plasma in them as determined by Ferric Reducing Ability of Plasma (FRAP) and the effect was found to be dose-dependent. The oral administration of IM6E in diabetic rats normalized almost all the deregulated biochemical markers like liver enzymes, lipids and significantly decreased higher blood glucose levels with increasing insulin levels as compared to diabetic control. The best concentration of IM6E was found to be 300 mg/kg b.w after 21 days of experimentation. The intra-peritoneal glucose tolerance test (IPGTT) in diabetic rats responded very well to IM6E treatment and 100 mg/kg.b.w. behaved almost like the administration of 0.5U insulin/kg bw, and thus indicating the insulinotropic nature of IM6E. Our findings clearly reveal the use of IM6E for diabetes management and at the same it possesses great potential when combined with voglibose to ameliorate diabetes and its associated complications to a greater extent due to synergistic effects as compared to monotherapy. However, more clinical trials need to be performed before recommending IM6E as an anti-diabetic alternative medicine.     

Pharmacological support to anti-arthritic prospective of physostigmine: a new approach

Rheumatoid arthritis (RA) is a slowly progressing inflammatory autoimmune disease. Several features are involved in the RA pathogenesis in addition to environmental and genetic factors. Previously it has been reported that acetyl cholinesterase (AChE) activity is enhanced in old age and may contribute in the progression of RA. The current experimental work was projected to assess the activity of physostigmine (a cholinesterase inhibitor) for treatment of RA. In vitro and in vivo approaches were used for such evaluation. However, enzyme linked immunosorbent assays (ELISA) was performed to determine the concentrations of Prostaglandins E2 (PGE2) and tumor necrosis factor-α in arthritic rats after treatment with physostigmine. Moreover, anti-oxidant assays were employed to calculate the level of super oxide dismutase (SOD) and catalase peroxidase (CAT) in tissue of treated animals. The results claimed the dose dependent protective and stabilizing effect of physostigmine on denaturation of albumin (egg and bovine serum) protein and human red blood cell membrane, respectively, through in vitro studies. Furthermore, the physostigmine (10 and 20 mg/kg) significantly (p?<?0.001) reduced the swelling of paw after induction of arthritis with formaldehyde or complete Freund’s adjuvant (CFA) as compared to arthritic control animals. Moreover, significant (p?<?0.001) reduction in the levels of inflammatory markers (PGE2 and TNF-α) at doses of 10 and 20 mg/kg of physostigmine has been observed in ELISA test. Likewise, there was a prominent rise in levels of SOD and CAT in animals treated with physostigmine. These findings pharmacologically conclude the anti-arthritic effect of physostigmine.

     

An unusual cause of ischemia after coronary bypass grafting!!

Coronary subclavian steal syndrome is an uncommon cause of ischemia recurrence after coronary artery bypass grafting. Endovascular treatment of subclavian artery stenosis or occlusion is increasingly common and appears to offer a safe and effective alternative to surgical revascularization. We report a case of recurrent angina after coronary artery bypass grafting for critical subclavian artery stenosis. The anomalous origin of the vertebral artery from the aortic arch was an indication for endovascular treatment. We discuss the diagnostic difficulties and the management pitfalls of subclavian artery angioplasty in this syndrome.