Research

Primary Pneumococcal Peritonitis can be the first presentation of a familial complement factor I deficiency.

Clin Exp Immunol. 2020 Jul 08;:

Authors: Ugrinovic S, Firth H, Kavanagh D, Gouliouris T, Gurugama P, Baxendale H, Lachmann PJ, Kumararatne D, Gkrania-Klotsas E

Abstract
Primary pneumococcal peritonitis is a rare infection that has been described in women but has not been previously linked with immunodeficiency. The complement system plays a central role in immune defense against Streptococcus pneumoniae and, in order to evade complement attack, pneumococci have evolved a large number of mechanisms that limit complement mediated opsonization and subsequent phagocytosis.We investigated an apparently immunocompetent woman with primary pneumococcal peritonitis and identified a family with deficiency for complement factor I. Primary pneumococcal peritonitis should be considered a possible primary immunodeficiency presentation.

PMID: 32640035 [PubMed – as supplied by publisher]

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Clinical and Mutation Description of the First Iranian Cohort of Infantile Inflammatory Bowel Disease: The Iranian Primary Immunodeficiency Registry (IPIDR).

Immunol Invest. 2020 Jul 07;:1-15

Authors: Rahmani F, Rayzan E, Rahmani MR, Shahkarami S, Zoghi S, Rezaei A, Aryan Z, Najafi M, Rohlfs M, Jeske T, Aflatoonian M, Chavoshzadeh Z, Farahmand F, Motamed F, Rohani P, Alimadadi H, Mahdaviani A, Mansouri M, Tavakol M, Vanderberg M, Kotlarz D, Klein C, Rezaei N

Abstract
We describe a cohort of 25 Iranian patients with infantile inflammatory bowel disease (IBD), 14 (56%) of whom had monogenic defects. After proper screening, patients were referred for whole exome sequencing (WES). Four patients had missense mutations in the IL10 RA, and one had a large deletion in the IL10 RB. Four patients had mutations in genes implicated in host:microbiome homeostasis, including TTC7A deficiency, and two patients with novel mutations in the TTC37 and NOX1. We found a novel homozygous mutation in the SRP54 in a deceased patient and the heterozygous variant in his sibling with a milder phenotype. Three patients had combined immunodeficiency: one with ZAP-70 deficiency (T+B+NK-), and two with atypical SCID due to mutations in RAG1 and LIG4. One patient had a G6PC3 mutation without neutropenia. Eleven of the 14 patients with monogenic defects were results of consanguinity and only 4 of them were alive to this date.

PMID: 32633164 [PubMed – as supplied by publisher]

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A new case of congenital ficolin-3 deficiency with primary immunodeficiency.

Expert Rev Clin Immunol. 2020 Jul 07;:

Authors: Babaha F, Abolhassani H, Hamidi Esfahani Z, Yazdani R, Aghamohammadi A

Abstract
OBJECTIVES: Human Ficolin-3 (FCN3) is an oligomeric-structured lectin encoded by the FCN3 gene with a pivotal role in the lectin complement pathway. It has anti-microbial activities against bacterial and viral infections and restrains opportunistic pathogens. Mutation in the FCN3 gene is associated with variable clinical manifestations particularly immunologic (infections and autoimmunity) and neurologic complications.
METHODS: In this study, we report a 5-year-old boy with a biallelic mutation in the FCN3 gene using clinical and immunological and genetic evaluations (whole exome sequencing).
RESULTS: Our case is the first national and the eighth case worldwide with a confirmed frameshift mutation associated with Ficolin-3 deficiency. He manifested refractory seizures since early infancy, meningitis, pyelonephritis and was diagnosed with severe primary immunodeficiency.
CONCLUSION: Our case and literature review indicate Ficolin-3 deficiency should be considered in early-onset, premature neonate with a bacterial infection, neurological manifestation and systemic lupus erythematosus like presentations.

PMID: 32634042 [PubMed – as supplied by publisher]

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Prophylaxis of Acute Attacks with a Novel Short-term Protocol in Hereditary Angioedema Patients Requiring Periodontal Treatment.

Oral Health Prev Dent. 2020 Apr 01;18(2):355-361

Authors: Ramaglia L, Isola G, Matarese G, Bova M, Quattrocchi P, Iorio-Siciliano V, Guida A

Abstract
PURPOSE: C1-inhibitor (C1-INH) related hereditary angioedema (C1-INH-HAE) is a rare pathological condition caused by a deficiency or a functional alteration of serum protein C1-INH. Clinical manifestations are represented by recurrent, potentially life-threatening episodes of cutaneous or mucosal oedema. The present study analysed the effectiveness of a specific short-term prophylaxis protocol for the management of C1-INH-HAE patients requiring chronic periodontitis treatment.
MATERIALS AND METHODS: Ten consecutive C1-INH-HAE patients with mild to moderate chronic periodontitis were treated by non-surgical periodontal therapy with a full-mouth scaling approach (FMS) in two sessions 24 h apart. All patients underwent a short-term prophylaxis protocol of acute attacks based on the association of attenuated androgen (danazol), from 5 days before the first FMS session to 2 days after the second FMS session, and C1-INH concentrate given 1 h before the first FMS session. Patients were examined for periodontal changes over a 6-month period.
RESULTS: None of patients developed complications or oedema up to 1 week postoperatively. Compared to baseline, scaling and root planing (SRP) treatment yielded, at 6 months, a statistically significant improvement in probing depth (PD) (baseline: 5.24 mm ± 0.85 mm vs 6 months: 2.96 ± 0.31 mm), clinical attachment level (CAL) (baseline: 5.46 ± 0.81 vs 6 months: 3.89 ± 0.38 mm), full-mouth bleeding score (FMBS) (baseline: 27.6 ± 2.2% vs 6 months: 18.5 ± 2.1%) and in full-mouth plaque score (FMPS) (baseline: 28.6 ± 2.4% vs 6 months: 21.66 ± 3.3%).
CONCLUSIONS: This study showed the clinical effectiveness of the reported prophylaxis protocol in preventing acute attacks in HAE patients requiring non-surgical periodontal treatment, with no complications up to 1 week after FMS.

PMID: 31268048 [PubMed – indexed for MEDLINE]

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STAT1 Gain-of-Function with Refractory Hemophagocytic Lymphohistiocytosis.

Ann Allergy Asthma Immunol. 2020 Jul 03;:

Authors: Eng V, Zomorodian TJ, Samant SA, Maarup TJ, Sheikh J

PMID: 32629017 [PubMed – as supplied by publisher]

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A Novel Pathogenic Variant in CARMIL2 (RLTPR) Causing CARMIL2 Deficiency and EBV-Associated Smooth Muscle Tumors.

Front Immunol. 2020;11:884

Authors: Yonkof JR, Gupta A, Rueda CM, Mangray S, Prince BT, Rangarajan HG, Alshahrani M, Varga E, Cripe TP, Abraham RS

Abstract
CARMIL2 deficiency is a rare combined immunodeficiency (CID) characterized by defective CD28-mediated T cell co-stimulation, altered cytoskeletal dynamics, and susceptibility to Epstein Barr Virus smooth muscle tumors (EBV-SMTs). Case reports associated with EBV-SMTs are limited. We describe herein a novel homozygous CARMIL2 variant (c.1364_1393del) in two Saudi Arabian male siblings born to consanguineous parents who developed EBV-SMTs. CARMIL2 protein expression was significantly reduced in CD4+ T cells and CD8+ T cells. T cell proliferation on stimulation with soluble (s) anti-CD3 or (s) anti-CD3 plus anti-CD28 antibodies was close to absent in the proband, confirming altered CD28-mediated co-signaling. CD28 expression was substantially reduced in the proband’s T cells, and was diminished to a lesser degree in the T cells of the younger sibling, who has a milder clinical phenotype. Defects in both T and B cell compartments were observed, including absent central memory CD8+ T cells, and decreased frequencies of total and class-switched memory B cells. FOXP3+ regulatory T cells (Treg) were also quantitatively decreased, and furthermore CD25 expression within the Treg subset was substantially reduced. These data confirm the pathogenicity of this novel loss-of-function (LOF) variant in CARMIL2 and expand the genotypic and phenotypic spectrum of CIDs associated with EBV-SMTs.

PMID: 32625199 [PubMed – in process]

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Haploidentical Hematopoietic Stem Cell Transplantation for XIAP Deficiency: a Single-Center Report.

J Clin Immunol. 2020 Jul 05;:

Authors: Yang J, Zhu GH, Wang B, Zhang R, Jia CG, Yan Y, Ma HH, Qin MQ

Abstract
PURPOSE: X-linked inhibitor of apoptosis (XIAP) deficiency caused by mutations in the XIAP/BIRC4 gene is a rare inherited primary immunodeficiency also known as X-linked lymphoproliferative syndrome type 2 (XLP2). Hematopoietic stem cell transplantation (HSCT) is currently the only curative strategy available. However, few studies of haploidentical HSCT have been published regarding the outcomes in patients with this syndrome.
METHODS: We evaluated the XIAP gene analysis and clinical characteristics of four Chinese patients with XIAP who underwent haploidentical HSCT.
RESULTS: The mutations in the two of four patients had not yet been reported in the literature. All of the patients had recurrent hemophagocytic lymphohistiocytosis but did not have a good matched donor and underwent haploidentical HSCT at BCH in China between September 2016 and December 2018. All four patients received antithymocyte globulin with fludarabine-based regimens. Two patients underwent reduced intensity conditioning (RIC), and the other two received modified myeloablative conditioning (MAC) regimens. Three of the four patients survived. Three patients experienced complications with mixed chimerism. One of the four patients who underwent RIC had early graft loss and then developed grade IV acute graft-versus-host disease (GVHD) after donor lymphocyte infusion with bone marrow. The two patients who received MAC survived with no or mild GVHD, even though one of them developed hepatic veno-occlusive disease in the early stage of transplantation.
CONCLUSIONS: Haploidentical HSCT may be a treatment option for patients with XIAP deficiency who lack a good matched donor. More studies are needed to determine whether modified MAC with reduced toxicity is more suitable for haploidentical transplantation.

PMID: 32627096 [PubMed – as supplied by publisher]

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