Research

Autoantibodies against BAFF, APRIL or IL21 – an alternative pathogenesis for antibody-deficiencies?

June 28, 2017 By Manish Butte

Autoantibodies against BAFF, APRIL or IL21 – an alternative pathogenesis for antibody-deficiencies?

BMC Immunol. 2017 Jun 26;18(1):34

Authors: Pott MC, Frede N, Wanders J, Hammarström L, Glocker EO, Glocker C, Tahami F, Grimbacher B

Abstract
BACKGROUND: The ability of anti-cytokine antibodies to play a disease-causing role in the pathogenesis of immunodeficiencies is widely accepted. The aim of this study was to investigate whether autoantibodies against BAFF (important B cell survival signal), APRIL (important plasma cell survival signal), or Interleukin-21 (important cytokine for immunoglobulin class switch) present an alternative mechanism for the development of the following primary antibody deficiencies (PADs): common variable immune deficiency (CVID) or selective IgA deficiency (sIgAD).
RESULTS: Two hundred thirty-two sera from patients with PADs were screened for autoantibodies against cytokines by ELISA. Statistical data analysis yielded a significant difference (p < 0.01) between the healthy donor sera and both PAD cohorts. The analysis was deepened by subdividing the patient collective into groups with distinct B cell phenotypes but no significant differences were found. For selected sera with notable high ELISA-read outs functional analysis ensued. Anti-BAFF and anti-APRIL antibodies were further examined by a B cell survival assay, whilst the functional relevance of putative anti-IL-21 autoantibodies was investigated by means of a STAT3 phosphorylation assay. However, the results of these experiments revealed no discernible functional effect.
CONCLUSION: Whilst statistical analysis of ELISA results showed significant differences between patients and healthy controls, in our set of patients functional tests yielded no evidence for an involvement of autoantibodies against BAFF, APRIL, or IL-21 in the pathogenesis of CVID or sIgAD.

PMID: 28651547 [PubMed – in process]

A novel mother-to-child human T-cell leukaemia virus type 1 (HTLV-1) transmission model for investigating the role of maternal anti-HTLV-1 antibodies using orally infected mother rats.

June 27, 2017 By Manish Butte

A novel mother-to-child human T-cell leukaemia virus type 1 (HTLV-1) transmission model for investigating the role of maternal anti-HTLV-1 antibodies using orally infected mother rats.

J Gen Virol. 2017 Apr;98(4):835-846

Authors: Murakami Y, Hasegawa A, Ando S, Tanaka R, Masuda T, Tanaka Y, Kannagi M

Abstract
Human T-cell leukaemia virus type 1 (HTLV-1) is a human retrovirus that is a causative agent of adult T-cell leukaemia/lymphoma (ATL) and is mainly transmitted from an infected mother to her child via breastfeeding. Such an HTLV-1 infection during childhood is believed to be a risk factor for ATL development. Although it has been suggested that an increased proviral load (PVL), a higher titre of antibody (Ab) in the infected mother and prolonged breastfeeding are associated with an increased risk of mother-to-child transmission (MTCT), the mechanisms underlying MTCT of HTLV-1 remain largely unknown. In this study, we developed an MTCT model using orally HTLV-1-infected rats that have no Ab responses against viral antigens, such as Gag and Env. In this model, HTLV-1 could be transmitted from the infected mother rats to their offspring at a high rate (50-100 %), and the rate of MTCT tended to be correlated with the PVL of the infected mother rats. Furthermore, passive immunization of uninfected adult rats and an infected mother rat with a rat anti-HTLV-1 Env gp46-neutralizing mAb was unable to suppress primary oral HTLV-1 infection to the adult rats and vertical HTLV-1 transmission to the offspring, respectively. Our findings indicate that this MTCT model would be useful to investigate not only the mechanisms of MTCT but also the role of anti-HTLV-1 Ab in MTCT of HTLV-1. They also provide some information on the role of maternal Abs in MTCT, which should be considered when designing a strategy for prevention of MTCT of HTLV-1.

PMID: 28150581 [PubMed – indexed for MEDLINE]

Yield of Cytology Surveillance After High-Grade Vulvar Intraepithelial Neoplasia or Cancer.

June 24, 2017 By Manish Butte

Yield of Cytology Surveillance After High-Grade Vulvar Intraepithelial Neoplasia or Cancer.

J Low Genit Tract Dis. 2017 Jul;21(3):193-197

Authors: Kuroki LM, Frolova AI, Wu N, Liu J, Powell M, Thaker PH, Massad LS

Abstract
OBJECTIVES: The aim of the study was to estimate the risk of high-grade cervical and vaginal intraepithelial neoplasia (CIN/VAIN 2+) and cancer among women treated surgically for high-grade vulvar intraepithelial neoplasia (HGVIN) and vulvar cancer.
MATERIALS AND METHODS: We performed a retrospective cohort study of women who underwent surgery for HGVIN/vulvar cancer between 2006 and 2010. Univariate and multivariate analyses using stepwise selection were used to identify correlates of abnormal cytology after treatment for VIN and vulvar cancer.
RESULTS: Among 191 women under surveillance for a median of 3.7 years who underwent treatment for HGVIN/vulvar cancer, primary vulvar lesions included VIN 2 (10, 5%), VIN 3 (102, 53%), and carcinoma (79, 41%). During follow-up, 71 (37%) had abnormal cytology, including 47 (25%) low grade, 23 (12%) high grade, and 1 (0.5%) carcinoma. Subsequent risk for VAIN 2+ was 11% (6/57) after previous hysterectomy and 8% for CIN 2+ (10/124) with intact cervix. Overall risk for CIN 3+ was 5%. Correlates of high-grade cytology after treatment for HGVIN/vulvar cancer included nonwhite race (odds ratio [OR] = 3.3, 95% CI = 1.50-7.36), immunodeficiency (OR = 4.2, 95% CI = 1.76-9.94), and previous abnormal cytology (OR = 2.7, 95% CI = 1.29-5.78). Stepwise multivariate analysis revealed immunosuppression as the only significant correlate of high-grade cytology after vulvar treatment (adjusted OR = 3.7, 95% CI = 1.26-10.83).
CONCLUSIONS: Women with HGVIN/cancer should have cervical/vaginal cytology before vulvar surgery. Those with a negative cervical or vaginal cytology result should undergo cytology testing at 1- to 3-year intervals, based on the threshold for CIN 3+ set forth by the American Society for Colposcopy and Cervical Pathology.

PMID: 28644191 [PubMed – in process]

A Review on Defects of Dendritic Cells in Common Variable Immunodeficiency.

June 24, 2017 By Manish Butte

A Review on Defects of Dendritic Cells in Common Variable Immunodeficiency.

Endocr Metab Immune Disord Drug Targets. 2017 Jun 13;:

Authors: Sharifi L, Tavakolinia N, Kiaee F, Rezaie N, Mohsenzadegan M, Shariat M, Yazdani R, Mirshafiey A, Aghamohammadi A, Azizi G

Abstract
BACKGROUND AND OBJECTIVES: Common variable immunodeficiency (CVID) is the most important primary that is associated with clinical complications including recurrent infections, malignancy and autoimmune diseases. The genetic cause of CVID is mostly unknown and only a few genetic causes are identified. The various options are proposed for determining the etiology of CVID patients, such as T- and B-cell defects, Toll-like receptors (TLRs) impairments, altered cytokine production as well as blemished dendritic cells (DCs). The patients with CVID show a reduction in number and frequency of DCs in blood, an altered expression of cell surface molecules, and defective activation through toll-like receptors (TLRs). Also loss of IFNa has a critical role in B-cell impairments of CVID patients. The aim of this review is to collect under one umbrella, all the recent knowledge about DCs defects of CVID patients.
METHODS: This review covers basic information about physiology of DCs followed by reports of DCs situation in CVID.
CONCLUSION: According to the results of researches assessing DCs frequency and function in CVID, the roll of DCs in the pathogenesis of CVID cannot be ruled out. The article is expected to encourage the researchers to do comprehensive researches about complex connections between DCs and other immune cells in CVID.

PMID: 28641569 [PubMed – as supplied by publisher]

Progressive multifocal leukoencephalopathy in a patient with lymphoma and presumptive hyper IgE syndrome.

June 24, 2017 By Manish Butte

Progressive multifocal leukoencephalopathy in a patient with lymphoma and presumptive hyper IgE syndrome.

J Neurovirol. 2017 Jun 22;:

Authors: Gocmen R, Acar NP, Cagdas D, Kurne A

Abstract
We, herein, report a 23-year-old male with a rare inherited immunodeficiency disease, hyperimmunoglobulin IgE syndrome (HIES), who developed progressive multifocal leukoencephalopathy (PML) and lymphoma simultaneously. Primary immunodeficiency of the patient has remained undiagnosed until adulthood. PML is a severe demyelinating disease of the central nervous system caused by John Cunningham virus. HIES is a rare, inherited immunodeficiency characterized by high serum levels of IgE, recurrent staphylococcal infection, eczema, and hypereosinophilia. PML may accompany primary immunodeficiency syndromes, but the association with HIES is exceedingly rare. We discuss the imaging findings, medical management, and a review of related literature on primary immunodeficiency cases complicating with PML.

PMID: 28643229 [PubMed – as supplied by publisher]

Risk management in providing specialized care for people living with AIDS.

June 24, 2017 By Manish Butte

Risk management in providing specialized care for people living with AIDS.

Rev Esc Enferm USP. 2016 Sep-Oct;50(5):838-845

Authors: Leadebal OD, Medeiros LB, Morais KS, Nascimento JA, Monroe AA, Nogueira JA

Abstract
OBJECTIVE: Analyzing the provision of actions related to managing clinical risk in managing specialized care for people living with AIDS.
METHOD: A cross-sectional study carried out in a reference outpatient clinic in Paraíba, with a sample of 150 adults with AIDS. Data were collected through primary and secondary sources using a structured questionnaire, analyzed using descriptive statistics, multiple correspondence analysis and logistic regression model to determine the association between “providing care” and “clinical risk.”
RESULTS: Actions with satisfactory provision express a biological care focus; the dimensions that most contributed to a satisfactory assessment of care provision were “clinical and laboratory evaluations” and “prevention and self-care incentivization”; 45.3% of participants were categorized into high clinical risk, 34% into average clinical risk, and 20.7% into low clinical risk; a positive association between providing care and clinical risk was found.
CONCLUSION: The need to use risk classification technologies to direct the planning of local care provision became evident considering its requirements, and thus qualifying the care provided in these areas.
OBJETIVO: Analisar a oferta de ações relacionadas ao manejo de risco clínico na gestão do cuidado especializado a pessoas vivendo com aids.
M?TODO: Estudo transversal realizado em ambulatório de referência na Paraíba, com amostra de 150 adultos com aids. Os dados foram coletados por meio de fontes primárias e secundárias utilizando-se de formulário estruturado, e analisados através de estatística descritiva, análise de correspondência múltipla e modelo de regressão logística para averiguar a associação entre “oferta” e “risco clínico”.
RESULTADOS: As ações de oferta satisfatória expressam foco biologicista do cuidado; as dimensões que mais contribuíram para o julgamento satisfatório da oferta foram “avaliação clínica e laboratorial” e “prevenção e estímulo ao autocuidado”; 45,3% dos participantes foram categorizados em risco clínico alto, 34% em risco clínico médio, e 20,7% em risco clínico baixo; e verificou-se associação positiva entre oferta e risco clínico.
CONCLUS?O: Ficou evidente a necessidade da utilização de tecnologias de classificação de risco para direcionar o planejamento da oferta local, considerando-se as necessidades, e assim qualificar o cuidado produzido nestes espaços.

PMID: 27982404 [PubMed – indexed for MEDLINE]

Hemophagocytic lymphohistiocytosis as presenting manifestation of profound combined immunodeficiency due to an ORAI1 mutation.

June 22, 2017 By Manish Butte

Hemophagocytic lymphohistiocytosis as presenting manifestation of profound combined immunodeficiency due to an ORAI1 mutation.

J Allergy Clin Immunol. 2017 Jun 17;:

Authors: Klemann C, Ammann S, Heizmann M, Fuchs S, Bode SF, Heeg M, Fuchs H, Lehmberg K, Zur Stadt U, Roll C, Vraetz T, Speckmann C, Lorenz MR, Schwarz K, Rohr J, Feske S, Ehl S

PMID: 28633876 [PubMed – as supplied by publisher]

Hemofagocitinė limfohistiocitozė: literatūros apžvalga.

June 21, 2017 By Manish Butte

Hemofagocitinė limfohistiocitozė: literatūros apžvalga.

Acta Med Litu. 2017;24(1):51-66

Authors: Bereikienė S, Rascon J

Abstract
HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS A LITERATURE REVIEW: Hemophagocytic lymphohistiocytosis is an immune dysregulatory syndrome that is associated with alteration in the immune response activation and inhibition balance. There are two basic forms of the syndrome: primary (genetic or familial) determined by genes mutations involved in immune cell interactions, and secondary or sporadic developing as a result of an infectious process. The exact genetic background of the secondary form is still unknown. These forms are characterized by same combination of specific hyperinflammatory reactions and clinical signs and symptoms. Discrimination between primary and secondary forms is often challenging due to the rarity of the pathology, a wide spectrum of clinical signs, and limited availability of specific tests. Etiopathogenetic treatment of the primary form is an urgent allogeneic hematopoietic stem cell transplantation, otherwise a fatal outcome is inevitable. Meanwhile, the approach to the secondary form depends on the clinical manifestation and the type of the infectious trigger. To rescue the patient, a timely diagnosis is crucial for prompt administration of appropriate treatment. Treatment of hemophagocytic lymphohistiocytosis is complicated by the high incidence of treatment-related mortality and the propensity to relapse. Keywords: hemophagocytis lymphohistiocytosis, immunodeficiency, diagnostic criteria.

PMID: 28630593 [PubMed – in process]

Sclerosing cholangitis and intracranial lymphoma in a child with classical Wiskott-Aldrich syndrome.

June 21, 2017 By Manish Butte

Sclerosing cholangitis and intracranial lymphoma in a child with classical Wiskott-Aldrich syndrome.

Pediatr Blood Cancer. 2017 Jan;64(1):106-109

Authors: Vignesh P, Suri D, Rawat A, Lau YL, Bhatia A, Das A, Srinivasan A, Dhandapani S

Abstract
Patients with Wiskott-Aldrich syndrome (WAS) are predisposed to malignancy and autoimmunity in addition to infections. We report a male child with WAS, who had presented with recurrent pneumonia, eczema, thrombocytopenia, autoimmune hemolytic anemia, and vasculitic skin lesions. Genetic analysis revealed a classical genotype WAS 155C>T; R41X. At 2 years of follow-up, he developed persistent headache and progressive hepatomegaly. Brain imaging showed a mass in the right frontal region, which on histopathology was shown to be high-grade non-Hodgkin lymphoma. Magnetic resonance cholangiopancreatography showed features of sclerosing cholangitis. This report extends the clinical spectrum and highlights unusual manifestations of sclerosing cholangitis and intracranial lymphoma in a patient with WAS.

PMID: 27566838 [PubMed – indexed for MEDLINE]

Single Cell-Based Vector Tracing in Patients with ADA-SCID Treated with Stem Cell Gene Therapy.

June 20, 2017 By Manish Butte

Single Cell-Based Vector Tracing in Patients with ADA-SCID Treated with Stem Cell Gene Therapy.

Mol Ther Methods Clin Dev. 2017 Sep 15;6:8-16

Authors: Igarashi Y, Uchiyama T, Minegishi T, Takahashi S, Watanabe N, Kawai T, Yamada M, Ariga T, Onodera M

Abstract
Clinical improvement in stem cell gene therapy (SCGT) for primary immunodeficiencies depends on the engraftment levels of genetically corrected cells, and tracing the transgene in each hematopoietic lineage is therefore extremely important in evaluating the efficacy of SCGT. We established a single cell-based droplet digital PCR (sc-ddPCR) method consisting of the encapsulation of a single cell into each droplet, followed by emulsion PCR with primers and probes specific for the transgene. A fluorescent signal in a droplet indicates the presence of a single cell carrying the target gene in its genome, and this system can clearly determine the ratio of transgene-positive cells in the entire population at the genomic level. Using sc-ddPCR, we analyzed the engraftment of vector-transduced cells in two patients with severe combined immunodeficiency (SCID) who were treated with SCGT. Sufficient engraftment of the transduced cells was limited to the T cell lineage in peripheral blood (PB), and a small percentage of CD34(+) cells exhibited vector integration in bone marrow, indicating that the transgene-positive cells in PB might have differentiated from a small population of stem cells or lineage-restricted precursor cells. sc-ddPCR is a simplified and powerful tool for the detailed assessment of transgene-positive cell distribution in patients treated with SCGT.

PMID: 28626778 [PubMed – in process]