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1.
Artigo em Inglês | MEDLINE | ID: mdl-32060950

RESUMO

BACKGROUND: There is no data regarding the prevalence of malignancies in patients with primary immunodeficiency (PID) in Turkey. Along with the prevalence of malignancy, we aimed to present the types of malignancy and define the underlying immune deficiency of the patients. METHOD: Between the years 1992 and 2018 years, from 5 tertiary immunology clinics, fifty-nine patients with PID who developed malignancy were included. All patients were evaluated for demographics, clinical features, and prognosis. RESULTS: The prevalence of malignancy in our cohort was detected as 0.9% (59/6392). The male to female ratio was 1.8 (38/21), and the median age of patients was 14 years (range: 1.5 - 51). The median age at diagnosis of malignancy was 10 years (range: 1.5 - 51). Ataxia-telangiectasia was the most frequent PID in patients with malignancy (n= 19, 32.2%), and non-Hodgkin lymphoma was the most common malignancy (n= 32, 51.6%). The rate of malignancy in DOCK8 deficiency (n=7/43, 16.3%) was higher than AT (n=19/193, 9.8%), WAS (n=2/22, 9.1%) and CVID (n=11/205, 5.4%). EBV quantitative PCR was positive in 16 out of 53 patients (30.2%). Three patients had secondary malignancies. Remission was achieved in 26 patients (44.1%). However, 31 patients (52.5%) died. Two patients (3.4%) are still on chemotherapy. CONCLUSION: This study is the largest cohort investigating the association of malignancy in patients with PID in Turkey. While lymphoid malignancies were the most common malignancy and observed more frequently in AT patients, the risk for malignancy was higher in patients with DOCK8 deficiency then AT.

2.
Rheumatol Int ; 40(1): 161-168, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31273456

RESUMO

Familial Mediterranean fever (FMF) is the most common monogenic auto-inflammatory disease characterized by recurrent attacks of fever and serositis. Although colchicine is the first line treatment in FMF, 5-10% of patients do not respond to colchicine. Canakinumab, an anti-IL-1ß monoclonal antibody, has been reported to be effective and safe in colchicine-resistant FMF patients, but the adequate duration and interval of treatment is still a matter of debate. Aim of this study was to evaluate the success of the standardized treatment protocol for canakinumab applied in our Pediatric Rheumatology Department in colchicine-resistant FMF cases with a review of the literature. Nine patients included in this study had indications for canakinumab use as colchicine resistance and recurrent corticosteroid need for pleural/pericardial effusions. Canakinumab was administered monthly for 6 months (initial treatment), bimonthly for 6 months (maintenance treatment), then treatment was discontinued. For the patients who developed a new attack after one-year treatment period, canakinumab was readministered with 3-month intervals (continuation treatment). The mean follow-up time beginning from the first canakinumab injection was 24.3 ± 10.2 (6-33) months. None of the patients had an attack during the first-year treatment. Four of the patients developed an attack 9.0 ± 2.9 (6-12) months after discontinuation of treatment and switched to the continuation treatment period, with no more attacks. We suggest that this standard protocol may be used successfully in colchicine-resistant FMF patients.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31887391

RESUMO

BACKGROUND: Recent findings strongly support hematopoietic stem cell transplantation (HSCT) in patients with severe presentation of LPS-responsive beige-like anchor protein (LRBA) deficiency, but long-term follow-up and survival data beyond previous patient reports or meta-reviews are scarce for those patients who do not receive a transplant. OBJECTIVE: This international retrospective study was conducted to elucidate the longitudinal clinical course of patients with LRBA deficiency who do and do not receive a transplant. METHOD: We assessed disease burden and treatment responses with a specially developed immune deficiency and dysregulation activity score, reflecting the sum and severity of organ involvement and infections, days of hospitalization, supportive care requirements, and performance indices. RESULTS: Of 76 patients with LRBA deficiency from 29 centers (median follow-up, 10 years; range, 1-52), 24 underwent HSCT from 2005 to 2019. The overall survival rate after HSCT (median follow-up, 20 months) was 70.8% (17 of 24 patients); all deaths were due to nonspecific, early, transplant-related mortality. Currently, 82.7% of patients who did not receive a transplant (43 of 52; age range, 3-69 years) are alive. Of 17 HSCT survivors, 7 are in complete remission and 5 are in good partial remission without treatment (together, 12 of 17 [70.6%]). In contrast, only 5 of 43 patients who did not receive a transplant (11.6%) are without immunosuppression. Immune deficiency and dysregulation activity scores were significantly lower in patients who survived HSCT than in those receiving conventional treatment (P = .005) or in patients who received abatacept or sirolimus as compared with other therapies, and in patients with residual LRBA expression. Higher disease burden, longer duration before HSCT, and lung involvement were associated with poor outcome. CONCLUSION: The lifelong disease activity, implying a need for immunosuppression and risk of malignancy, must be weighed against the risks of HSCT.

4.
Case Reports Immunol ; 2019: 1902817, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31467740

RESUMO

DIRA (deficiency of the IL-1Ra) is a rare condition that usually presents in the neonatal period. Patients with DIRA present with systemic inflammation, respiratory distress, joint swelling, pustular rash, multifocal osteomyelitis, and periostitis. Previously, we reported a patient with a novel mutation in IL1RN with a healthy neonatal period, a late-onset of pustular dermatosis, inflammatory arthritis, and excellent response to canakinumab treatment. Herein, we are presenting a new case of late-onset DIRA syndrome, carrying a different mutation and showing different clinical findings. This patient is the first one in the literature with the inflammatory arthritis, nail psoriasis, and onychomycosis and with her remarkable response to monoclonal antibodies. The case responded well and fully recovered after treatment with adalimumab, but not with canakinumab. The DIRA disease can lead to death from multiple organ failures and if recognized early, the treatment with replacement of the deficient protein with biologic agents induces rapid and complete remission. Therefore, clinical symptoms should be learned exactly by the pediatricians, pediatric rheumatologists, and immunologists; and molecular analysis targeting this defect must be performed as early as possible.

5.
J Allergy Clin Immunol Pract ; 7(8): 2790-2800.e15, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31238161

RESUMO

BACKGROUND: LPS-responsive beige-like anchor (LRBA) deficiency presents with susceptibility to infections, autoimmunity, and lymphoproliferation. The long-term efficacy of cytotoxic T-lymphocyte-associated antigen 4-immunoglobulin (abatacept) as targeted therapy for its immune dysregulatory features remains to be established. OBJECTIVE: To determine the clinical and immunologic features of LRBA deficiency and long-term efficacy of abatacept treatment in controlling the different disease manifestations. METHODS: Twenty-two LRBA-deficient patients were recruited from different immunology centers and followed prospectively. Eighteen patients on abatacept were evaluated every 3 months for long-term clinical and immunologic responses. LRBA expression, lymphocyte subpopulations, and circulating T follicular helper cells were determined by flow cytometry. RESULTS: The mean age of the patients was 13.4 ± 7.9 years, and the follow-up period was 3.4 ± 2.3 years. Recurrent infections (n = 19 [86.4%]), immune dysregulation (n = 18 [81.8%]), and lymphoproliferation (n = 16 [72.7%]) were common clinical features. The long-term benefits of abatacept in 16 patients were demonstrated by complete control of lymphoproliferation and chronic diarrhea followed by immune dysregulation, most notably autoimmune cytopenias. Weekly or every other week administration of abatacept gave better disease control compared with every 4 weeks. There were no serious side effects related to the abatacept therapy. Circulating T follicular helper cell frequencies were found to be a reliable biomarker of disease activity, which decreased on abatacept therapy in most subjects. However, high circulating T follicular helper cell frequencies persisted in 2 patients who had a more severe disease phenotype that was relatively resistant to abatacept therapy. CONCLUSIONS: Long-term abatacept therapy is effective in most patients with LRBA deficiency.

6.
Indian J Clin Biochem ; 34(1): 95-100, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30728679

RESUMO

Anti-beta-2-glycoprotein I antibodies (anti-ß2GPI) which are the main antiphospholipid antibodies that characterize the autoimmune "antiphospholipid syndrome" are pathogenic and are contributing to thrombosis. We aimed to evaluate the presence and the diagnostic importance of these antibodies in children with different rheumatologic diseases with or without thrombosis risk. A total of 100 children with different rheumatologic diseases evaluated retrospectively. The mean anti-ß2GPI IgG (p = 0.108), IgA (p = 0.547), and IgM (p = 0.807) levels showed no statistically significant difference between different diagnosis groups. But anti-ß2GPI IgA and IgM levels were higher in SLE patient group. The mean anti-ß2GPI IgG (p = 0.375), IgA (p = 0.811), and IgM (p = 0.276) levels were not also showed difference between disease groups with/without predisposition to thrombosis even though concentrations were higher in thrombosis group. In children with rheumatological complaints, anti-ß2GPI antibody measurements should not be the first diagnostic criteria if vasculitis is not thought as the primary defect underlying the clinical symptoms.

7.
Scand J Immunol ; 89(2): e12737, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30506560

RESUMO

Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by susceptibility to bacterial and fungal infections resulting from the inadequacy of phagocytic leucocytes to produce reactive oxygen radicals. CGD is a genetically heterogeneous disease with an X-linked recessive (XR-CGD) form caused by mutations in the CYBB (OMIM #300481) gene encoding the gp91(phox) protein, and an autosomal recessive (AR-CGD) form caused by mutations in the CYBA (OMIM #608508), NCF1 (OMIM #608512), NCF2 (OMIM #608515) and NCF4 (OMIM #601488) genes encoding p22(phox), p47(phox), p67(phox) and p40(phox), respectively. The genetic mutation of one of the cytosolic p47phox/p67phox proteins and membrane-bound gp91phox/p22phox proteins, which constitutes the NADPH oxidase enzyme complex, causes the disease. In this study, we evaluated the clinical, laboratory and genetic findings and the prognostic effects of molecular inheritance of our 24 CGD cases (14 XR, 10 autosomal recessive-AR). Consanguinity (three XR and all AR cases) showed statistically significant relationship with the type of hereditary inheritance (P < 0.001). 83% patients had an infection since early infancy. The mean age of initiation of symptoms was earlier in XR cases, and 78% patients had respiratory tract infections. Bone marrow transplantation was performed in five XR cases (two ex) and four AR (one ex) cases. Three of nine XR and two of six AR cases deceased on medical follow-up. In countries especially with high consanguinity rates, the early diagnosis for appropriate prophylactic treatment of CGD is quietly important to avoid from recurrent severe infections, early death and fatal complications of late transplantation.


Assuntos
Consanguinidade , Doença Granulomatosa Crônica/imunologia , NADPH Oxidases/metabolismo , Adolescente , Idade de Início , Transplante de Medula Óssea , Criança , Pré-Escolar , Feminino , Seguimentos , Genes Recessivos/genética , Genes Ligados ao Cromossomo X/genética , Doença Granulomatosa Crônica/epidemiologia , Doença Granulomatosa Crônica/genética , Humanos , Masculino , Mutação/genética , NADPH Oxidase 2/genética , Espécies Reativas de Oxigênio/metabolismo , Estudos Retrospectivos , Resultado do Tratamento , Turquia/epidemiologia
8.
Case Reports Immunol ; 2018: 6897935, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30405923

RESUMO

When caring for patients with life-limiting diseases, improving survival and optimizing quality of life are the primary goals. For patients with X-linked hyper-IgM syndrome (XHIGM), the treatment modality has to be decided for a particular patient regarding hematopoietic stem cell transplantation or intravenous immunoglobulin replacement therapy with P. jiroveci prophylaxis. A seven-year-old male patient was admitted with recurrent upper and lower respiratory tract infections and recurrent otitis media. His initial immunologic evaluation revealed low IgG and normal IgA and IgM levels with normal lymphocyte phenotyping and inadequate specific antibody responses. He was diagnosed as common variable immunodeficiency and began to receive intravenous immunoglobulin (IVIG) (0.5 gm/kg) with four-week intervals. During follow-up for 23 years under IVIG therapy, he was extremely well and never had severe infections. In 2017, targeted next generation sequencing was performed in order to understand his molecular pathology. A previously described hemizygous c.31C>T(p.Arg11Ter) mutation was found in CD40LG gene. The mother was heterozygous carrier for this mutation and his sister did not have any mutation. Flow cytometric analysis for CD40LG expression on activated T cells showed highly decreased, but not absent, CD40LG expression. In conclusion, diagnostic delay is a clinical problem for patients with CD40LG deficiency, because of low or normal IgM levels, showing that all the hypogammaglobulinemic patients, not only with high serum IgM levels, but also with normal to low IgM levels, have to be examined for CD40LG expression on activated T lymphocytes. Secondly, type of CD40LG mutations leads to enormous interpatient variations regarding serum IgM levels, CD40LG levels on activated T cells, age at diagnosis, severity of clinical findings, and follow-up therapies with or without hematopoietic stem cell therapy.

9.
JMM Case Rep ; 5(10): e005167, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30479781

RESUMO

Introduction: LPS-responsive beige-like anchor (LRBA) protein deficiency is a disease of immune dysregulation with autoimmunity affecting various systems. Case Presentation: Two male siblings with a novel LRBA mutation had different primary findings at admission: the younger sibling had chronic early-onset diarrhoea and the elder one had autoimmune haemolytic anaemia. During long-term follow-up for IPEX phenotype, both developed hypogammaglobulinaemia, enteropathy and lung involvement. The patients partially responded to immunosuppressive therapies. A homozygous c.2496C>A, p.Cys832Ter (p.C832*) mutation in the LRBA gene causing a premature stop codon was detected. After molecular diagnosis, abatacept, as a target-specific molecule, was used with promising results. Conclusion: LRBA deficiency is a recently defined defect, with variable presentations in different patients; a single, definitive treatment option is thus not yet available.

10.
Pediatr Int ; 60(10): 911-917, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30103264

RESUMO

BACKGROUND: Primary immunodeficiency disorder (PID), being a chronic disorder, may increase the prevalence of psychopathologies, but there are few studies on the effect of disease-related factors on psychopathology in this population. The aim of this study was therefore to assess and compare three groups: children with PID who receive i.v. immunoglobulin treatment; children with juvenile idiopathic arthritis (JIA); and healthy controls with respect to their mental health status. METHODS: Forty-four children with PID, 32 children with JIA and 30 healthy controls, underwent psychiatric evaluation. The Childhood Depression Inventory and the screen for child anxiety-related emotional disorders questionnaire were completed by the participants. The child behavior checklist was completed by the mothers of the participants. In addition, disease-related factors were identified. RESULTS: The frequency of mood disorders between the three groups differed. There was no difference between the PID and JIA groups with respect to the prevalence of mood disorders and other psychopathologies. The disease-related factors were associated with the frequency of mood disorder in PID patients. CONCLUSION: The rate of psychopathology was similar in patients with PID and JIA and higher than the controls. Some of the disease-related factors were associated with the frequency of mood disorders in the PID patients.


Assuntos
Síndromes de Imunodeficiência/psicologia , Transtornos Mentais/etiologia , Adolescente , Artrite Juvenil/psicologia , Estudos de Casos e Controles , Criança , Efeitos Psicossociais da Doença , Estudos Transversais , Feminino , Humanos , Masculino , Transtornos Mentais/diagnóstico , Transtornos Mentais/epidemiologia , Escalas de Graduação Psiquiátrica , Fatores de Risco
11.
Avicenna J Med Biotechnol ; 10(3): 192-195, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30090215

RESUMO

Background: The Transmembrane Activator and Calcium modulator ligand Interactor (TACI), encoded by TNFRSF13B/TACI gene, is mutated in some patients with Common Variable Immunodeficiency (CVID) and IgA Deficiency (IgAD). The purpose of the study was to investigate for the first time in Turkish patients the prevalence of TNFRSF13B alterations in CVID, selective and partial IgAD patients. Methods: Forty two CVID, 36 selective IgAD, 34 partial IgAD and 25 healthy controls were included. All patients were examined for TNFRSF13B gene mutations by PCR. Results: The percentages of TNFRSF13B mutations in CVID, selective and partial IgAD patients were 7.1, 2.7 and 2.9%, respectively. No disease causing TNFRSF13B mutation in healthy controls was found. Patients with TACI mutations had recurrent respiratory tract infections. None of them experienced autoimmunity, bronchiectasis or granulomatous disease. In conclusion, TNFRSF13B mutations were present not only in CVID patients, but also in IgAD cases. Conclusion: Modifier genes as well as their combination with other genetic or environmental factors may play an important role in the development of the immunodeficiency phenotype.

13.
Int J Immunopathol Pharmacol ; 32: 2058738418779458, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29978731

RESUMO

Common variable immunodeficiency (CVID) and immunoglobulin A deficiency (IgAD) are the most prevalent primary immunodeficiency disorders. High rates of familial inheritance have been described in CVID and IgAD, but it is unknown in different ethnic populations. We aimed to determine the prevalence of familial cases and whether they showed more severe clinical characteristics than sporadic ones in Turkish patients. A total of 40 CVID and 70 IgAD patients and their 251 first-degree relatives (FDRs) were evaluated. Demographic, clinical, and laboratory data were reviewed. A familial case was defined as a patient with at least one affected FDR (A-FDR). The rate of parental consanguinity was 19.1%. There were 37 familial cases (37/110) (33.6%) with at least one A-FDR. There were 48 A-FDRs who had immunoglobulins lower than age-related normals (48/251) (19.1%). Pulmonary infections were significantly higher in familial cases. To our knowledge, this study includes the highest number of CVID/IgAD patients and their FDRs in literature. Familial cases are at least 30% of the IgAD and CVID patients, and they have more frequent lower respiratory tract infections than sporadic ones, so these patients have to be evaluated depending on their being familial or sporadic for better management. The risk of carrying any immunologic alterations in relatives of patients with IgAD and CVID is approximately 20%. Although most A-FDRs are asymptomatic, considering the risk of progression to CVID by age, we highly recommend routine screening for FDRs.


Assuntos
Imunodeficiência de Variável Comum/epidemiologia , Consanguinidade , Deficiência de IgA/epidemiologia , Imunoglobulina A/sangue , Adulto , Imunodeficiência de Variável Comum/genética , Imunodeficiência de Variável Comum/imunologia , Feminino , Hereditariedade , Humanos , Deficiência de IgA/genética , Deficiência de IgA/imunologia , Masculino , Pessoa de Meia-Idade , Linhagem , Turquia
14.
Int J Rheum Dis ; 21(2): 502-509, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28941122

RESUMO

OBJECTIVE: Periostin has been shown to be involved in bone anabolism through the regulation of Wnt-ß-catenin signaling. It may be one of the pathogenic mechanisms in syndesmophyte formation in ankylosing spondylitis (AS). The aim of this study was to evaluate serum periostin levels in patients with AS and to assess relationships among biomarkers of bone formation and periostin in disease outcomes, particularly radiographic changes. METHODS: Ninety-seven consecutive AS patients (78% male) and 48 healthy controls (75% male) were included in the study. Serum periostin, dickkopf-1 (DKK-1), sclerostin and vascular endothelial growth factor (VEGF) levels were measured using commercially available enzyme-linked immunosorbent assay kits. Disease-related characteristics of patients were assessed using Ankylosing spondylitis disease activity score - C-reactive protein (ASDAS-CRP), Bath AS Disease Activity Index, Bath AS Functional Index and Bath AS metrology index. Radiographs were scored using the modified New York criteria and modified Stokes AS spinal score (mSASSS). RESULTS: Compared with control subjects, patients with AS had significantly lower serum levels of periostin (P < 0.001) and sclerostin (P < 0.001), but higher serum levels of VEGF (P < 0.001) and high-sensitivity CRP (P < 0.001). Serum periostin (P = 0.005) and sclerostin levels (P = 0.016) were significantly lower in patients with very high disease activity according to ASDAS-CRP. Current age (P = 0.009), age at symptom onset (P = 0.021) and hip joint involvement (P = 0.012) were independently associated with the development of syndesmophyte, in contrast to biomarkers of bone metabolism that we evaluated. CONCLUSION: Our results suggest that periostin is down-regulated in AS patients with highly active disease and may contribute to disease pathogenesis through an interaction with Wnt signaling.


Assuntos
Osso e Ossos/metabolismo , Moléculas de Adesão Celular/sangue , Osteogênese , Espondilite Anquilosante/sangue , Via de Sinalização Wnt , Adulto , Biomarcadores/sangue , Proteínas Morfogenéticas Ósseas/sangue , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/fisiopatologia , Proteína C-Reativa/análise , Estudos de Casos e Controles , Estudos Transversais , Regulação para Baixo , Feminino , Marcadores Genéticos , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Masculino , Pessoa de Meia-Idade , Espondilite Anquilosante/diagnóstico por imagem , Espondilite Anquilosante/fisiopatologia , Fator A de Crescimento do Endotélio Vascular/sangue , Adulto Jovem
15.
J Clin Lab Anal ; 32(1)2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28383134

RESUMO

BACKGROUND: Functional studies besides routine laboratory tests for the definitive diagnosis of T lymphocyte disorders with isolated T or combined T/B-cell immunodeficiencies are important. We hereby summarized our experience with a carboxyfluorescein diacetate succinimidyl ester (CFSE)-based assay for the assessment of mitogenic T-cell proliferation responses in primary immunodeficiency (PID) patients who have not been diagnosed yet or genetically analyzed, but classified as probably having T-cell defects. METHODS: Unclassified patients (n=46) and controls (n=25) were evaluated for T-cell disorders with CFSE-based assay. RESULTS: CD3+ blast cells after PHA-L stimulation were significantly lower in patients (31.1±28.8) than controls (67.9±8.79; P<.001). Nine patients with low and four patients with normal CD3 values had severely decreased blastic transformation. The proliferation response decreased mostly in combined immunodeficiency group. Sixteen of them had impaired proliferation responses. Appropriate molecular genetical analyses were planned after thorough evaluation of each patient. CONCLUSIONS: In vitro lymphocyte cell proliferation analysis by CFSE method is a reliable and practical choice for the assessment of mitogenic T lymphocyte responses in yet unclassified PID patients for targeting further genetical analyses.


Assuntos
Proliferação de Células/fisiologia , Fluoresceínas/análise , Corantes Fluorescentes/análise , Síndromes de Imunodeficiência/diagnóstico , Succinimidas/análise , Linfócitos T/citologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Citometria de Fluxo , Fluoresceínas/química , Fluoresceínas/metabolismo , Corantes Fluorescentes/química , Corantes Fluorescentes/metabolismo , Humanos , Lactente , Masculino , Succinimidas/química , Succinimidas/metabolismo , Linfócitos T/química , Linfócitos T/metabolismo , Linfócitos T/fisiologia
16.
Case Reports Immunol ; 2017: 2846928, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29259832

RESUMO

Chronic Mucocutaneous Candidiasis (CMC) is the chronic, recurrent, noninvasive Candida infections of the skin, mucous membranes, and nails. A 26-month-old girl was admitted with the complaints of recurrent oral Candidiasis, diarrhea, and respiratory infections. Candida albicans grew in oral mucosa swab. CMV and EBV DNA titers were elevated. She had hypergammaglobulinemia; IgE level, percentages of lymphocyte subgroups, and in vitro T-cell proliferation responses were normal. She had parenchymal nodules within the lungs and a calcific nodule in the liver. Chronic-recurrent infections with different pathogens leading to significant morbidity suggested combined immunodeficiency, CMC, or Mendelian susceptibility to mycobacterial diseases. Genetic analysis revealed a predefined heterozygous gain-of-function mutation (GOF) (c.1154 C>T, p.Thr385Met) in the gene coding STAT1 molecule. Hematopoietic stem cell transplantation (HSCT) was planned because of severe recurring infections. Patients with STAT1 GOF mutations may exhibit diverse phenotypes including infectious and noninfectious findings. HSCT should be considered as an early treatment option before permanent organ damage leading to morbidity and mortality develops. This case is presented to prompt clinicians to consider STAT1 GOF mutations in the differential diagnosis of patients with chronic Candidiasis and recurrent infections with multiple organisms, since these mutations are responsible for nearly half of CMC cases reported.

17.
Turk Pediatri Ars ; 52(3): 138-144, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29062247

RESUMO

AIM: Susceptibility to mycobacterial diseases is observed in some primary immunodeficiency diseases. In this study, we aimed to evaluate mycobacterial infections in primary immunodeficiency diseases. MATERIAL AND METHODS: Patients under follow-up by Ege University Pediatric Immunology Department for severe combined and combined immunodeficiencies, interleukin 12/ interferon gamma receptor deficiency, nuclear factor kappa-beta essential modulator deficiency and chronic granulomatosis disease were evaluated retrospectively in terms of the frequency and characteristics of mycobacterial infections using a questionnaire form for demographic properties, clinical features and laboratory tests. RESULTS: A diagnosis of mycobacterial infection was made clinically in a total of 25 patients including five (11.3%) of 45 patients who had severe combined immune deficiency, 12 (52.3%) of 21 patients who had chronic granulomatous disease, four patients (100%) who had interferon gamma receptor 2 partical deficiency, two patients (100%) who had interleukin 12 receptor beta 1 deficiency and one patient (100%) who had nuclear factor kapa-beta essential modulator deficiency. Mycobacterium strain could be typed in 14 (33%) of these 25 patients including Mycobacterium bovis, Mycobacterium chelonea, Mycobacterium elephantis, Mycobacterium fortuitum, and Mycobacterium tuberculosis. All patients were treated with anti-tuberculosis therapy. Thirty-six percent of these 25 patients underwent hematopoietic stem cell transplantation. Eight patients (five before, three after transplantation) died. CONCLUSIONS: Non-tuberculosis mycobacteria including mainly Mycobacterium bovis were observed with a higher rate compared to Mycobacterium tuberculosis in primary immunodeficiencies, especially in those affecting the interleukin 12/interferon gamma pathway. Early diagnosis of primary immunodeficiencies with neonatal screening program and preventing administration of the Bacille Calmette-Guerin vaccine in these patients is important.

18.
Inflamm Bowel Dis ; 23(12): 2109-2120, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28930861

RESUMO

BACKGROUND: In contrast to adult-onset inflammatory bowel disease (IBD), where many genetic loci have been shown to be involved in complex disease etiology, early-onset IBD (eoIBD) and associated syndromes can sometimes present as monogenic conditions. As a result, the clinical phenotype and ideal disease management in these patients often differ from those in adult-onset IBD. However, due to high costs and the complexity of data analysis, high-throughput screening for genetic causes has not yet become a standard part of the diagnostic work-up of eoIBD patients. METHODS: We selected 28 genes of interest associated with monogenic IBD and performed targeted panel sequencing in 71 patients diagnosed with eoIBD or early-onset chronic diarrhea to detect causative variants. We compared these results to whole-exome sequencing (WES) data available for 25 of these patients. RESULTS: Target coverage was significantly higher in the targeted gene panel approach compared with WES, whereas the cost of the panel was considerably lower (approximately 25% of WES). Disease-causing variants affecting protein function were identified in 5 patients (7%), located in genes of the IL10 signaling pathway (3), WAS (1), and DKC1 (1). The functional effects of 8 candidate variants in 5 additional patients (7%) are under further investigation. WES did not identify additional causative mutations in 25 patients. CONCLUSIONS: Targeted gene panel sequencing is a fast and effective screening method for monogenic causes of eoIBD that should be routinely established in national referral centers.


Assuntos
Diarreia/etiologia , Predisposição Genética para Doença , Doenças Inflamatórias Intestinais/genética , Idade de Início , Criança , Pré-Escolar , Doença Crônica , Feminino , Estudo de Associação Genômica Ampla , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Recém-Nascido , Masculino , Mutação , Sequenciamento Completo do Exoma
19.
Int J Immunopathol Pharmacol ; 30(2): 194-200, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28449602

RESUMO

In order to evaluate B-lymphocyte subsets of patients with primary immunodeficiencies, the normal values for national healthy children have to be used as a reference. Recently, B-cell co-receptor markers (CD19, CD21, and CD81) and CD20, CD22, and CD27 deficiencies have been reported in relation with different primary immunodeficiency diseases. The objective of this study was to establish national reference values for B-lymphocyte co-receptors and some surface markers, CD20, CD22, CD27, as well as classic lymphocyte subsets in the peripheral blood of healthy children. A total of 90 healthy children were included in this study. Complete blood counts were performed and cells with CD3, CD4, CD8, CD19, CD16/56, CD20, CD21, CD22, CD27, and CD81 surface markers were simultaneously detected by flow cytometry. The children were evaluated in three age subgroups, 0-1, 1-6, and >6 years, and minimum, maximum, mean, mean minus standard deviation, and 2.5-97.5 percentile values were all determined. By establishing reliable reference ranges for these surface markers, we hoped to help identifying and classifying some primary immunodeficiency patients, especially those defined as unclassified hypogammaglobulinemia and those without definite diagnosis.


Assuntos
Antígenos de Superfície/sangue , Proteínas de Membrana/sangue , Adolescente , Antígenos de Superfície/imunologia , Linfócitos B/imunologia , Criança , Pré-Escolar , Feminino , Voluntários Saudáveis , Humanos , Síndromes de Imunodeficiência/sangue , Síndromes de Imunodeficiência/imunologia , Lactente , Recém-Nascido , Masculino , Proteínas de Membrana/imunologia , Valores de Referência , Turquia
20.
Case Reports Immunol ; 2017: 2676403, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28168067

RESUMO

Chronic granulomatous disease (CGD) is a primary immune deficiency causing predisposition to infections with specific microorganisms, Aspergillus species and Staphylococcus aureus being the most common ones. A 16-year-old boy with a mutation in CYBB gene coding gp91phox protein (X-linked disease) developed a liver abscess due to Staphylococcus aureus. In addition to medical therapy, surgical treatment was necessary for the management of the disease. A 30-month-old girl with an autosomal recessive form of chronic granulomatous disease (CYBA gene mutation affecting p22phox protein) had invasive aspergillosis causing pericarditis, pulmonary abscess, and central nervous system involvement. The devastating course of disease regardless of the mutation emphasizes the importance of early diagnosis and intervention of hematopoietic stem cell transplantation as soon as possible in children with CGD.

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