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Prevalence of Feline Immunodeficiency Virus and Toxoplasma gondii in Feral Cats on St. Kitts, West Indies.

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Prevalence of Feline Immunodeficiency Virus and Toxoplasma gondii in Feral Cats on St. Kitts, West Indies.

Vet Sci. 2021 Jan 21;8(2):

Authors: Chi X, Fang K, Koster L, Christie J, Yao C

Abstract
Toxoplasma gondii (T. gondii) is a cosmopolitan protozoan parasite that infects all warm-blooded species including humans. The definitive hosts of T. gondii are felid vertebrates including the domestic cat. Domestic cats shed oocysts for approximately two weeks in their feces after the primary infection. It has been shown that feline immunodeficiency virus (FIV) positive cats have a higher prevalence of and a higher titer of antibodies to T. gondii than those of FIV-negative cats. The main purposes of this study were to determine FIV prevalence and to investigate the oocysts shedding in FIV-positive and FIV-negative feral cats on St. Kitts. Fecal samples were collected from feral cats while their FIV statues were determined using a commercial SNAP kit. Total fecal DNA of each cat was tested for the presence of T. gondii DNA using a polymerase chain reaction (PCR) consistently detecting one genome equivalent. A FIV-positive status was detected in 18 of 105 (17.1%, 95% confidence interval (CI): 9.9%-24.3%) feral cats sampled. Furthermore, males were three times more likely to be FIV positive than females (p = 0.017) with an odds ratio of 3.93 (95% CI: 1.20-12.89). Adults were found to have at least twice the prevalence of FIV compared to cats younger than one year of age (p = 0.056) with an odds ratio of 3.07 (95% CI: 0.94-10.00). Toxoplasma gondii DNA was not detected in the feces of any of the 18 FIV-positive (95% CI: 0%-0.18%) and 87 FIV-negative cats (95% CI: 0%-0.04%). A follow-up study with a much bigger sample size is needed to prove or disprove the hypothesis that FIV-positive cats have a higher prevalence of shedding T. gondii oocysts than FIV-negative cats.

PMID: 33494205 [PubMed]

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Bradykinin and oxidative stress in patients with hereditary angioedema due to C1 inhibitor deficiency.

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Bradykinin and oxidative stress in patients with hereditary angioedema due to C1 inhibitor deficiency.

Pol Arch Intern Med. 2020 02 27;130(2):79-88

Authors: Obtułowicz K, Góralska J, Bogdali A, Dyga W, Obtułowicz A, Myszkowska D, Ziemianin M, Gruca A, Solnica B, Czarnobilska E

Abstract
INTRODUCTION: Hereditary angioedema (HAE) is a rare autosomal dominant disease caused by genetic dysfunction of C1 inhibitor (C1-INH) due to mutations in the SERPING1 gene. The disorder is mediated mainly by bradykinin. The clinical course of the disease is varied and not related to genetic changes.
OBJECTIVES: We aimed to evaluate redox homeostasis of peripheral blood mononuclear cells (PBMCs) in patients with HAE due to C1-INH deficiency (C1 INH HAE) by measuring the levels of reactive oxygen species (ROS) of PBMCs as well as plasma advanced glycation end products (AGEs) and advanced oxidation protein products (AOPPs). We also aimed to assess the effect of bradykinin on ROS levels.
PATIENTS AND METHODS: We enrolled 30 adults with C1-INH-HAE and 15 healthy individuals. The levels of ROS were measured by flow cytometry, while the plasma levels of AGEs and AOPPs were determined spectrophotometrically by enzyme‑ linked immunosorbent assays.
RESULTS: Basal and hydrogen peroxide (H2O2)-induced ROS levels were higher in patients with HAE when compared with controls (P = 0.002 and P = 0.001, respectively), indicating abnormalities in redox homeostasis. Plasma AOPP and AGE levels were similar in both groups. Bradykinin reduced basal and H2O2-induced ROS generation in PBMCs only in patients with HAE (P = 0.03).
CONCLUSIONS: The higher basal and H2O2-induced ROS levels in patients with C1 INH HAE indicate redox imbalance. However, by reducing basal and H2O2-induced ROS levels, bradykinin shows antioxidant action in this disorder.

PMID: 31933486 [PubMed – indexed for MEDLINE]

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Sideroblastic anaemia, Immunodeficiency, Periodic Fevers, and developmental delay (SIFD) presenting as systemic inflammation with arthritis.

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Sideroblastic anaemia, Immunodeficiency, Periodic Fevers, and developmental delay (SIFD) presenting as systemic inflammation with arthritis.

Rheumatology (Oxford). 2021 Jan 25;:

Authors: Maccora I, Ramanan AV, Vergnano S, Roderick MR

PMID: 33493307 [PubMed – as supplied by publisher]

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Malabsorption Due to Chronic Giardiasis as a Presenting Symptom of Common Variable Immunodeficiency.

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Malabsorption Due to Chronic Giardiasis as a Presenting Symptom of Common Variable Immunodeficiency.

Cureus. 2020 Dec 21;12(12):e12201

Authors: Sousa D, Neto Gonçalves T, Marto N, Horta AB

Abstract
Common variable immunodeficiency (CVID) is a primary immunodeficiency that presents with a broad spectrum of clinical manifestations. We report the case of a 33-year-old man, initially referred to the outpatient internal medicine clinic for anemia. At the evaluation, the patient complained of diarrhea and unintentional weight loss for the last six months. He had no known medical conditions, but his previous medical history highlighted recurrent respiratory infections since childhood and also oral ulcers. The investigation identified iron-deficiency anemia caused by a malabsorption syndrome due to chronic giardiasis (Giardia lamblia cysts identified in fecal culture and Giardia lamblia trophozoites identified in the villi epithelium). Further investigation revealed bilateral bronchiectasis and splenomegaly. Suspecting CVID, a serum protein electrophoresis was performed, which showed a flattening of the gamma region, corresponding to a severe deficit of immunoglobulin (Ig) G, IgA, and IgM. A deficiency in the production of IgG in response to immunizations was confirmed, and the other causes of hypogammaglobulinemia were excluded. Therefore, a diagnosis of CVID was established. Malabsorption due to chronic giardiasis is a rare cause of iron deficiency anemia and an unusual presentation of CVID.

PMID: 33489610 [PubMed]

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[Genetic analysis of a child with co-commitment progressive multifocal leukoencephalopathy and X-linked hyper IgM syndrome].

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[Genetic analysis of a child with co-commitment progressive multifocal leukoencephalopathy and X-linked hyper IgM syndrome].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2021 Jan 10;38(1):78-82

Authors: Li D, Li Q

Abstract
OBJECTIVE: To detect variant of the CD40L gene and infection of Jamestown Canyon virus (JCV) in a 7-year-and-9-month-old boy with co-commitment progressive multifocal leukoencephalopathy (PML) and X-linked hyper IgM syndrome (XHIGM).
METHODS: Peripheral blood samples of the child and his parents were collected for the extraction of genomic DNA. The 5 exons and exon/intronic boundaries of the CD40L gene were subjected to PCR amplification and sequencing. Suspected variants were analyzed by using bioinformatic software. The JCV gene was amplified from genomic DNA by nested PCR and sequenced.
RESULTS: The child was found to harbor a hemizygous c.506 A>C (p.Y169S) missense variant in exon 5 of the CD40L gene. The variant may affect the TNFH domain of the CD40L protein and result in structural instability and loss of hydrophobic interaction between CD40L and CD40. As predicted by PolyPhen2 and SIFT software, the variant was probably damaging (score = 1.00) and deleterious (score= -8.868). His mother was found to be a heterozygous carrier, while the same variant was not found in his father. Gel electrophoresis of the nested PCR product revealed presence of target JCV band, which was confirmed to be 99% identical with the JCV gene by sequencing.
CONCLUSION: The patient was diagnosed with co-commitment XHIGM and PML based on the testing of the CD40L gene and JCV infection.

PMID: 33423265 [PubMed – indexed for MEDLINE]

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Inhibitory effect of alpha-lipoic acid on mitochondrial dysfunction and interleukin-8 expression in interleukin-1beta-stimulated ataxia teleangiectasia fibroblasts.

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Inhibitory effect of alpha-lipoic acid on mitochondrial dysfunction and interleukin-8 expression in interleukin-1beta-stimulated ataxia teleangiectasia fibroblasts.

J Physiol Pharmacol. 2020 Feb;71(1):

Authors: Yoon J, Lee H, Lim JW, Kim H

Abstract
Ataxia telangiectasia (A-T) is an inherited neurodegenerative disease caused by mutation in the ataxia telangiectasia mutated (ATM) gene, leading to loss of function in the encoded protein ATM. Because ATM functions to reduce oxidative stress by up-regulating antioxidant enzymes, oxidative stress is a prevalent A-T phenotype and a mediator of the inflammation that drives A-T pathology. Reactive oxygen species (ROS) levels and the expression of pro-inflammatory cytokine interleukin-8 (IL-8) were higher in A-T cells than in normal cells. ROS are related to mitochondrial dysfunction and activation of nuclear factor kappa B (NF-κB) to induce IL-8 expression. Alpha-lipoic acid (α-LA), a naturally occurring thiol compound, shows an antioxidant effect in various cells. This study is aimed to determine if α-LA confers protection against NF-κB activation, IL-8 expression, and mitochondrial dysfunction in A-T cells which are exposed to the inflammatory cytokine IL-1β. A-T fibroblasts were treated with or without α-LA. The levels of intracellular and mitochondrial ROS, mRNA and protein levels of IL-8, mitochondrial membrane potential (MMP), ATP levels, and DNA binding activity of NF-κB were determined. As a result, IL-1β increased NF-κB activation, IL-8 expression, intracellular and mitochondrial ROS levels, but decreased MMP and ATP level in A-T cells. Pretreatment of A-T cells with α-LA inhibited IL-1β-induced activation of NF-κB, IL-8 expression, and mitochondrial dysfunction by reducing ROS levels. In conclusion, supplementation with α-LA may be beneficial for reducing the oxidative stress-induced mitochondrial dysfunction and IL-8 production associated with A-T.

PMID: 32554850 [PubMed – indexed for MEDLINE]

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Rheumatological manifestations in inborn errors of immunity.

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Rheumatological manifestations in inborn errors of immunity.

Pediatr Res. 2020 01;87(2):293-299

Authors: Köstel Bal S, Pazmandi J, Boztug K, Özen S

Abstract
Rare monogenetic diseases serve as natural models to dissect the molecular pathophysiology of the complex disease traits. Rheumatologic disorders by their nature are considered complex diseases with partially genetic origin, as illustrated by their heterogeneous genetic background and variable phenotypic presentation. Recent advances in genetic technologies have helped uncover multiple variants associated with disease susceptibility; however, a precise understanding of genotype-phenotype relationships is still missing. Inborn errors of immunity (IEIs), in addition to recurrent infections, may also present with autoimmune and autoinflammatory rheumatologic manifestations and have provided insights for understanding the underlying the principles of immune system homeostasis and mechanisms of immune dysregulation. This review discusses the rheumatologic manifestations in IEIs with overlapping and differentiating features in immunodeficiencies and rheumatologic disorders.

PMID: 31581173 [PubMed – indexed for MEDLINE]

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