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Reticular Dysgenesis and Mitochondriopathy Induced by Adenylate Kinase 2 Deficiency with Atypical Presentation.

November 4, 2020 By Manish Butte

Reticular Dysgenesis and Mitochondriopathy Induced by Adenylate Kinase 2 Deficiency with Atypical Presentation.

Sci Rep. 2019 10 31;9(1):15739

Authors: Ghaloul-Gonzalez L, Mohsen AW, Karunanidhi A, Seminotti B, Chong H, Madan-Khetarpal S, Sebastian J, Vockley CW, Reyes-Múgica M, Vander Lugt MT, Vockley J

Abstract
Reticular dysgenesis is an autosomal recessive form of severe combined immunodeficiency (SCID) that usually manifests in newborns. It is a unique example of an immune deficiency that is linked to dysfunctional mitochondrial energy metabolism and caused by adenylate kinase 2 (AK2) deficiency. It is characterized by an early differentiation arrest in the myeloid lineage, impaired lymphoid maturation, and sensorineural hearing loss. In this study, a novel AK2 homozygous mutation, c.622 T > C [p.Ser208Pro], was identified in an Old Order Amish patient through whole exome sequencing. Functional studies showed that the patient’s cells have no detectable AK2 protein, as well as low oxygen consumption rate (OCR), extracellular acidification rate (ECAR) and proton production rate (PPR). An increased production of reactive oxygen species, mitochondrial membrane permeability, and mitochondrial mass, and decreased ATP production, were also observed. The results confirm the pathogenicity of the AK2 mutation and demonstrate that reticular dysgenesis should be considered in Amish individuals presenting with immune deficiency. We also describe other pathophysiological aspects of AK2 deficiency not previously reported.

PMID: 31673062 [PubMed – indexed for MEDLINE]

Combined Immunodeficiency, Hemolytic Anemia, and Growth Retardation Secondary to a Homozygous Mutation in the NHEJ1 Gene.

November 4, 2020 By Manish Butte

Combined Immunodeficiency, Hemolytic Anemia, and Growth Retardation Secondary to a Homozygous Mutation in the NHEJ1 Gene.

J Pediatr Hematol Oncol. 2020 05;42(4):333-335

Authors: Al-Marhoobi R, Al-Musalhi M, Naseem SU, Wali Y, Alsayegh A, Al-Tamemi S

PMID: 31259832 [PubMed – indexed for MEDLINE]

Bladder Artery Embolization for Massive Hematuria Treatment in a Patient With Ataxia-Telangiectasia Acute Lymphoblastic Leukemia.

November 4, 2020 By Manish Butte

Bladder Artery Embolization for Massive Hematuria Treatment in a Patient With Ataxia-Telangiectasia Acute Lymphoblastic Leukemia.

J Pediatr Hematol Oncol. 2020 05;42(4):316-318

Authors: Bahadir A, Oguz Ş, Erduran E, Dinç H, Yalçin Cömert HS, Bahat Özdogan E, Kaya G

Abstract
Ataxia-telangiectasia (AT) is a hereditary recessive autosomal disorder following a course of progressive cerebellar ataxia, and oculocutaneous telangiectasia. Disease-specific telangiectasias are generally localized in the oculocutaneous region, while telangiectasias located within the bladder are rarely seen in patients with AT. The patient who had been followed-up with a diagnosis of AT since the age of 3 years was later diagnosed with acute lymphoblastic leukemia at the age of 8 years. The patient developed hematuria approximately in the 29th month of treatment. The cystoscopy revealed regions of extensive hemorrhagic telangiectasis, which was interpreted as the bladder involvement of AT. The case presented here underwent several cycles of intravesical steroid and tranexamic acid treatments and intravesical cauterization procedures, but the patient was unresponsive to all medical treatment approaches. The patient was consequently evaluated by an interventional radiology unit for a selective arterial embolization. The patient’s hematuria resolved after embolization. Bladder wall telangiectasia may, on rare occasions, develop in patients with AT, and can result in life-threatening hemorrhages. We also suggest that a selective arterial embolectomy can be safely carried out in pediatric patients with treatment-resistant intravesical bleeding.

PMID: 30933018 [PubMed – indexed for MEDLINE]

Nodular Lymphoid Hyperplasia of the Rectum in a Patient With Primary Immunodeficiency.

November 3, 2020 By Manish Butte

Nodular Lymphoid Hyperplasia of the Rectum in a Patient With Primary Immunodeficiency.

Am J Gastroenterol. 2020 Oct 28;:

Authors: Santos-Antunes J, Carneiro F, Macedo G

PMID: 33136564 [PubMed – as supplied by publisher]

Treatment of Chronic Granulomatous Disease-Related Pulmonary Aspergillus Infection in Late Pregnancy.

November 3, 2020 By Manish Butte

Treatment of Chronic Granulomatous Disease-Related Pulmonary Aspergillus Infection in Late Pregnancy.

Open Forum Infect Dis. 2020 Oct;7(10):ofaa447

Authors: Johnson JA, Pearson JC, Kubiak DW, Dionne B, Little SE, Wesemann DR

Abstract
Chronic granulomatous disease (CGD) is a primary immunodeficiency syndrome that results in increased risk for bacterial and fungal infections, as well as inflammatory/autoimmune complications. While CGD historically has been associated with early death in childhood, the life expectancy and morbidity of patients with CGD have greatly improved. Many patients with CGD now survive well into adulthood, and data on adult cohorts of patients with CGD have been published. However, reports of pregnancy management, complications, and outcomes for patients with CGD are sparse. In addition, management of invasive fungal infections, including use of newer triazole antifungals, during pregnancy has not been well described. We report a case of fungal lung infection in a pregnant woman with CGD, diagnosed during her second trimester, which was treated with multiple antifungal agents, including more than 12 weeks of isavuconazole therapy, resulting in resolution of infection and delivery of a healthy newborn at term.

PMID: 33134418 [PubMed]

Adult-Onset ANCA-Associated Vasculitis in SAVI: Extension of the Phenotypic Spectrum, Case Report and Review of the Literature.

November 3, 2020 By Manish Butte

Adult-Onset ANCA-Associated Vasculitis in SAVI: Extension of the Phenotypic Spectrum, Case Report and Review of the Literature.

Front Immunol. 2020;11:575219

Authors: Staels F, Betrains A, Doubel P, Willemsen M, Cleemput V, Vanderschueren S, Corveleyn A, Meyts I, Sprangers B, Crow YJ, Humblet-Baron S, Liston A, Schrijvers R

Abstract
STING-associated vasculopathy with onset in infancy (SAVI) is an autosomal dominant disorder due to gain-of-function mutations in STING1, also known as TMEM173, encoding for STING. It was reported as a vasculopathy of infancy. However, since its description a wider spectrum of associated manifestations and disease-onset has been observed. We report a kindred with a heterozygous STING mutation (p.V155M) in which the 19-year-old proband suffered from isolated adult-onset ANCA-associated vasculitis. His father suffered from childhood-onset pulmonary fibrosis and renal failure attributed to ANCA-associated vasculitis, and died at the age of 30 years due to respiratory failure. In addition, an overview of the phenotypic spectrum of SAVI is provided highlighting (a) a high phenotypic variability with in some cases isolated manifestations, (b) the potential of adult-onset disease, and (c) a novel manifestation with ANCA-associated vasculitis.

PMID: 33133092 [PubMed – in process]

Flow Cytometry-Based Protocols for the Analysis of Human Plasma Cell Differentiation.

November 3, 2020 By Manish Butte

Flow Cytometry-Based Protocols for the Analysis of Human Plasma Cell Differentiation.

Front Immunol. 2020;11:571321

Authors: Khoenkhoen S, Ádori M, Pedersen GK, Karlsson Hedestam GB

Abstract
Humoral immunity is established after differentiation of antigen-specific B cells into plasma cells (PCs) that produce antibodies of relevant specificities. Defects in the development, activation, or differentiation of B cells severely compromises the immune response. Primary immunodeficiencies are often characterized by hypogammaglobulinemia and the inability to mount effective antigen-specific antibody responses, resulting in increased susceptibility to infections. After IgA deficiency, which is most often asymptomatic, common variable immunodeficiency (CVID) is the most prevalent symptomatic primary immunodeficiency, but in most cases the underlying genetic causes are unknown or their roles in disease pathogenesis are poorly understood. In this study, we developed a protocol for in vitro stimulation of primary human B cells for subsequent analyses of PC differentiation and antibody production. With this approach, we were able to detect a population of CD38+ IRF4+ Blimp-1+ cells committed to PC fate and IgG production, including when starting from cryopreserved samples. The application of functional assays to characterize PC differentiation and possible defects therein in B cells from patients suffering from primary antibody deficiencies with late B cell defects could increase our understanding of the disease pathophysiology and underlying mechanisms.

PMID: 33133085 [PubMed – in process]

COMMON VARIABLE IMMUNODEFICIENCY AMONG KYIV RESIDENTS: HETEROGENEITY OF MANIFESTATIONS (CLINICAL CASE REVIEW).

November 2, 2020 By Manish Butte

COMMON VARIABLE IMMUNODEFICIENCY AMONG KYIV RESIDENTS: HETEROGENEITY OF MANIFESTATIONS (CLINICAL CASE REVIEW).

Georgian Med News. 2020 Sep;(306):88-92

Authors: Tsaryk V, Swidro O, Plakhotna D, Gumeniuk N, Udovenko N

Abstract
Common variable immunodeficiency (CVID) is a kind of hypoimmunoglobulinemia of different spectrum with a dominant decrease of IgG with heterogeneity of clinical manifestations. In this publication, we provide an analysis of some world research sources on the diagnosis and treatment of the CVID and description of a clinical case of the CVID and the structural analysis of its frequency among primary immunodeficiencies in the adult population. We described the clinical case that demonstrates unusual manifestation of adult’s outcome of CVID with cellular immune deficiencies and immunoglobulin А deficiency and RAG-2 gene mutation. There is the prevalence of CVID and hereditary hypo-/agammaglobulinemias among the primary diagnosed immunodeficiencies in the inhabitants of the Kyiv region, that is given the severity of clinical manifestations and need of replacement immunoglobulinotherapy. As early prognostic marker for the development of CVID and other defects of antibodies an immunoglobulin E deficiency can be considered.

PMID: 33130653 [PubMed – in process]

Association between anthropometry and lifestyle factors and risk of B cell lymphoma: an exposome wide analysis.

November 1, 2020 By Manish Butte

Association between anthropometry and lifestyle factors and risk of B cell lymphoma: an exposome wide analysis.

Int J Cancer. 2020 Oct 31;:

Authors: Saberi Hosnijeh F, Casabonne D, Nieters A, Solans M, Naudin S, Ferrari P, Mckay JD, Benavente Y, Weiderpass E, Freisling H, Severi G, Boutron Ruault MC, Besson C, Agnoli C, Masala G, Sacerdote C, Tumino R, Huerta JM, Amiano P, Rodriguez-Barranco M, Bonet C, Barricarte A, Christakoudi S, Knuppel A, Bueno-de-Mesquita B, Schulze MB, Kaaks R, Canzian F, Späth F, Jerkeman M, Rylander C, Tjønneland A, Olsen A, Borch KB, Vermeulen R

Abstract
To better understand the role of individual and lifestyle factors in human disease, an exposome-wide association study was performed to investigate within a single study anthropometry measures and lifestyle factors previously associated with B-cell lymphoma (BCL). Within the European Prospective Investigation into Cancer and nutrition study, 2,402 incident BCL cases were diagnosed from 475,426 participants that were followed-up on average 14 years. Standard and penalized Cox regression models as well as principal component (PC) analysis were used to evaluate 84 exposures in relation to BCL risk. Standard and penalized Cox regression models showed a positive association between anthropometric measures and BCL and multiple myeloma/plasma cell neoplasm (MM). The penalized Cox models additionally showed the association between several exposures from categories of physical activity, smoking status, medical history, socioeconomic position, and diet and BCL and/or the subtypes. PC analyses confirmed the individual associations but also showed additional observations. The PC5 including anthropometry, was positively associated with BCL, diffuse large B-cell lymphoma (DLBCL), and MM. There was a significant positive association between consumption of sugar and confectionary (PC11) and follicular lymphoma risk, and an inverse association between fish and shellfish and Vitamin D (PC15) and DLBCL risk. The PC1 including features of the Mediterranean diet and diet with lower inflammatory score showed an inverse association with BCL risk, while the PC7, including dairy, was positively associated with BCL and DLBCL risk. Physical activity (PC10) was positively associated with DLBCL risk among women. This study provided informative insights on the etiology of BCL.

PMID: 33128820 [PubMed – as supplied by publisher]

Hypocalcemia and a Positive Metabolic Screen for Severe Combined Immunodeficiency in an 11-Day-Old Male With DiGeorge Syndrome.

October 31, 2020 By Manish Butte

Hypocalcemia and a Positive Metabolic Screen for Severe Combined Immunodeficiency in an 11-Day-Old Male With DiGeorge Syndrome.

Cureus. 2020 Sep 23;12(9):e10625

Authors: Ford J, Pena JM, Rainey SC

Abstract
22q11 deletion syndrome (22q11DS), also known as DiGeorge syndrome or velocardiofacial syndrome, is the most common human genetic microdeletion. Hypocalcemia secondary to hypoparathyroidism is a common finding in this condition and may present with seizures. We describe a case of an 11-day-old male presenting with hypocalcemic seizures and a positive newborn screen for severe combined immunodeficiency as the primary manifestations of 22q11DS. Given the potential for wide phenotypic variability, clinicians should maintain a high index of suspicion for this syndrome, especially in the neonate presenting with hypocalcemia.

PMID: 33123438 [PubMed]