Frequency of Gene Polymorphisms in Admixed Venezuelan Women with Recurrent Pregnancy Loss: Microsomal Epoxy Hydroxylase (rs1051740) and Enos (rs1799983).

Recurrent pregnancy loss (RPL) affects around 2% of women of reproductive age. Primary RPL is defined by ≥2 pregnancy losses and no normal birth delivery. In secondary RPL, the losses are after a normal pregnancy and delivery. Most cases have no clear aetiology, although primary cases are the most complex. Several gene single nucleotide polymorphisms (SNPs) have been associated with RPL. The frequency of some SNPs is increased in women suffering from RLP from Asian or Caucasian races; however, in admixed populations, the information on possible genetic links is scarce and contradictory. This study aimed to assess the frequency of two SNPs present in two different enzymes involved in medical conditions observed during pregnancy. It is a case-control study. Microsomal epoxy hydrolase (mEPH) is involved in detoxifying xenobiotics, is present in the ovaries, and is hormonally regulated. The endothelial nitric oxide synthase (NOS3) that forms nitric is involved in vascular tone. Two SNPs, rs1051740 (mEPH) and rs1799983 (NOS3), were assessed. The study included 50 controls and 63 primary RPL patients. The frequency of mutated alleles in both SNPs was significantly higher in patients (p < 0.05). Double-mutated homozygotes were encountered only in RPL patients (p < 0.05). Genetic polymorphisms rs1051740 and rs1799983 may be involved in primary RPL in the Venezuelan admix population. Genetic studies could provide crucial information on the aetiology of primary RPL.

Inflammation, Autoimmunity and Neurodegenerative Diseases, Therapeutics and Beyond.

Neurodegenerative disease (ND) incidence has recently increased due to improved life expectancy. Alzheimer's (AD) or Parkinson's disease (PD) are the most prevalent NDs. Both diseases are poly genetic, multifactorial and heterogenous. Preventive medicine, a healthy diet, exercise, and controlling comorbidities may delay the onset. After the diseases are diagnosed, therapy is needed to slow progression. Recent studies show that local, peripheral and age-related inflammation accelerates NDs' onset and progression. Patients with autoimmune disorders like inflammatory bowel disease (IBD) could be at higher risk of developing AD or PD. However, no increase in ND incidence has been reported if the patients are adequately diagnosed and treated. Autoantibodies against abnormal tau, ß amyloid and α- synuclein have been encountered in AD and PD and may be protective. This discovery led to the proposal of immune-based therapies for AD and PD involving monoclonal antibodies, immunization/ vaccines, pro-inflammatory cytokine inhibition and anti-inflammatory cytokine addition. All the different approaches have been analysed here. Future perspectives on new therapeutic strategies for both disorders are concisely examined.

Autoimmunity and Immunodeficiency in Severe SARS-CoV-2 Infection and Prolonged COVID-19.

SARS-CoV-2 causes the complex and heterogeneous illness known as COVID-19. The disease primarily affects the respiratory system but can quickly become systemic, harming multiple organs and leading to long-lasting sequelae in some patients. Most infected individuals are asymptomatic or present mild symptoms. Antibodies, complement, and immune cells can efficiently eliminate the virus. However, 20% of individuals develop severe respiratory illness and multiple organ failure. Virus replication has been described in several organs in patients who died from COVID-19, suggesting a compromised immune response. Immunodeficiency and autoimmunity are responsible for this impairment and facilitate viral escape. Mutations in IFN signal transduction and T cell activation are responsible for the inadequate response in young individuals. Autoantibodies are accountable for secondary immunodeficiency in patients with severe infection or prolonged COVID-19. Antibodies against cytokines (interferons α, γ and ω, IL1ß, IL6, IL10, IL-17, IL21), chemokines, complement, nuclear proteins and DNA, anticardiolipin, and several extracellular proteins have been reported. The type and titer of autoantibodies depend on age and gender. Organ-specific autoantibodies have been described in prolonged COVID-19. Their role in the disease is under study. Autoimmunity and immunodeficiency should be screened as risk factors for severe or prolonged COVID-19.