Research

Allergic and autoimmune disorders in families with selective IgA deficiency.

Turk J Med Sci. 2017 Apr 18;47(2):592-598

Authors: Erkoçoğlu M, Metin A, Kaya A, Özcan C, Akan A, Civelek E, Çapanoğlu M, Giniş T, Kocabaş CN

Abstract
BACKGROUND/AIM: IgA deficiency is the most common human primary immunodeficiency. The prevalence of allergic disorders and autoimmunity is thought to be increased in selective IgA deficiency (sIgAD). However, it is currently unclear if these disorders coincide within these families. We aimed to evaluate the frequency of allergic and autoimmune disorders in children with sIgAD and their first-degree relatives (FDRs).
MATERIALS AND METHODS: The study included 81 children diagnosed with sIgAD and 274 of their FDRs. The presence of allergic and autoimmune disorders was evaluated and serum antithyroglobulin and antithyroid peroxidase levels were measured in both patients and their first-degree relatives.
RESULTS: The mean age of the patients was 9.9 ± 3.9 years. Among the patients with sIgAD, 45.7% of them had at least one allergic disorder and 17.3% of them had at least one autoimmune disorder. The frequencies of asthma, allergic rhinitis, and eczema in the FDRs of sIgAD patients were 10.9%, 9.1%, and 7.7%, respectively. Among their FDRs, 14.6% had autoimmunity, compared to an estimate of 5% in the general population.
CONCLUSION: Increased frequency of allergic and autoimmune disorders in patients with sIgAD and their FDRs suggests a possible common predisposing genetic component for sIgAD and autoimmunity in these families.

PMID: 28425252 [PubMed – in process]

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Patient’s Experience in Pediatric Primary Immunodeficiency Disorders: Computerized Classification of Questionnaires.

Front Immunol. 2017;8:384

Authors: Mücke U, Klemann C, Baumann U, Meyer-Bahlburg A, Kortum X, Klawonn F, Lechner WM, Grigull L

Abstract
INTRODUCTION: Primary immunodeficiency disorders (PIDs) are a heterogeneous group of more than 200 rare diseases. Timely diagnosis is of uttermost importance. Therefore, we aimed to develop a diagnostic questionnaire with computerized pattern-recognition in order to support physicians to identify suspicious patient histories.
MATERIALS AND METHODS: Standardized interviews were conducted with guardians of children with PID. The questionnaire based on parental observations was developed using Colaizzis’ framework for content analysis. Answers from 64 PID patients and 62 controls were analyzed by data mining methods in order to make a diagnostic prediction. Performance was evaluated by k-fold stratified cross-validation.
RESULTS: The diagnostic support tool achieved a diagnostic sensitivity of up to 98%. The analysis of 12 interviews revealed 26 main phenomena observed by parents in the pre-diagnostic period. The questions were systematically phrased and selected resulting in a 36-item questionnaire. This was answered by 126 patients with or without PID to evaluate prediction. Item analysis revealed significant questions.
DISCUSSION: Our approach proved suitable for recognizing patterns and thus differentiates between observations of PID patients and control groups. These findings provide the basis for developing a tool supporting physicians to consider a PID with a questionnaire. These data support the notion that patient’s experience is a cornerstone in the diagnostic process.

PMID: 28424699 [PubMed – in process]

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Simian Immunodeficiency Virus Targeting of CXCR3(+) CD4(+) T Cells in Secondary Lymphoid Organs Is Associated with Robust CXCL10 Expression in Monocyte/Macrophage Subsets.

J Virol. 2017 Apr 19;:

Authors: Fujino M, Sato H, Okamura T, Uda A, Takeda S, Ahmed N, Shichino S, Shiino T, Saito Y, Watanabe S, Sugimoto C, Kuroda M, Ato M, Nagai Y, Izumo S, Matsushima K, Miyazawa M, Ansari AA, Villinger F, Mori K

Abstract
Glycosylation of Env defines pathogenic properties of SIV. We previously demonstrated that pathogenic SIVmac239 and live-attenuated, quintuple deglycosylated Env mutant (Δ5G) target CD4(+) T cells residing in different tissues during acute infection. SIVmac239 and Δ5G preferentially infected distinct CD4(+) T cells in secondary lymphoid organs (SLOs) and within the lamina propria of the small intestine, respectively (C. Sugimoto et al., J Virol 86:9323-9336, 2012). Herein, we studied the host responses relevant to SIV targeting of CXCR3(+)CCR5(+) CD4(+) T cells in SLOs. Genome-wide transcriptome analyses revealed that Th1-polarized inflammatory responses, defined by expression of CXCR3 chemokines, were distinctly induced in the SIVmac239-infected animals. Consistent with a robust expression of CXCL10, CXCR3(+) T cells were depleted from blood in the SIVmac239-infected animals. We also discovered that elevation of CXCL10 expression in blood and SLOs were secondary to the induction of CD14(+)CD16(+) monocytes and MAC387(+) macrophages, respectively. Since the significantly higher levels of SIV infection in SLOs occurred with a massive accumulation of infiltrated MAC387(+) macrophages, T cells, dendritic cells (DCs) and residential macrophages near high endothelial venules, the results highlight critical roles of innate/inflammatory responses in SIVmac239-infection. Restricted infection in SLOs by Δ5G also suggests that glycosylation of Env modulates innate/inflammatory responses elicited by cells of monocyte/macrophage/DCs lineage.IMPORTANCE We previously demonstrated that a pathogenic SIVmac239 and a live-attenuated, deglycosylated mutant Δ5G infected distinct CD4(+) T cell subsets in SLOs and the small intestine, respectively (C. Sugimoto et al., J Virol 86:9323-9336, 2012). Accordingly, infections with SIVmac239, but not with Δ5G, deplete CXCR3(+)CCR5(+)CD4(+) T (Th1) cells during the primary infection, thereby compromising the cellular immune response. Thus, we hypothesized that distinct host responses are elicited by the infections with 2 different viruses. We found that SIVmac239 induced distinctly higher levels of inflammatory-Th1 responses than Δ5G. In particular, SIVmac239 infection elicited a robust expression of CXCL10, a chemokine for CXCR3(+) cells, in CD14(+)CD16(+) monocytes and MAC387(+) macrophages, recently infiltrated in SLOs. In contrast, Δ5G infection elicited only modest inflammatory responses. These results suggest that the glycosylation of Env modulates the inflammatory/Th1 responses through the monocyte/macrophage subsets, and elicits marked differences in SIV infection and clinical outcomes.

PMID: 28424283 [PubMed – as supplied by publisher]

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Fibromyalgia in 300 adult index patients with primary immunodeficiency.

Clin Exp Rheumatol. 2017 Apr 19;

Authors: Barton JC, Bertoli LF, Barton JC, Acton RT

Abstract
OBJECTIVES: We sought to determine the prevalence and clinical and laboratory associations of fibromyalgia in adults with primary immunodeficiency (immunoglobulin (Ig) G subclass deficiency (IgGSD) and common variable immunodeficiency (CVID).
METHODS: We performed a retrospective analysis of these observations in 300 non-Hispanic white adult index patients with recurrent/severe respiratory tract infections and IgGSD or CVID: age; sex; IgGSD; fibromyalgia; chronic fatigue; autoimmune conditions (ACs); interstitial cystitis (IC); diabetes; body mass index; serum Ig isotypes; blood lymphocytes and subsets; and human leukocyte antigen (HLA)-A and -B types and haplotypes. We performed univariate comparisons, logistic multivariable regressions, and an analysis of covariance.
RESULTS: Mean age was 49 ± 12 (standard deviation) y. There were 246 women (82.0%). IgGSD was diagnosed in 276 patients (92.0%). Fifty-six patients had fibromyalgia (18.7%; female:male 13:1). Other characteristics included: chronic fatigue, 63.0%; aggregate ACs, 35.3%; Sjögren’s syndrome, 8.0%; IC, 3.0%; diabetes, 10.3%; and HLA-A*29, B*44 positivity, 9.7%. Prevalences of female sex; chronic fatigue; IC; and HLA-A*29, B*44 positivity were greater in patients with fibromyalgia. Logistic regression on fibromyalgia revealed three positive associations: chronic fatigue (p=0.0149; odds ratio 2.6 [95% confidence interval 1.2, 5.6]); Sjögren’s syndrome (p=0.0004; 5.2 [2.1, 13.2]); and IC (p=0.0232; 5.7 [1.3, 25.7]). In an analysis of covariance, there were significant interactions of chronic fatigue, Sjögren’s syndrome, and interstitial cystitis on fibromyalgia.
CONCLUSIONS: Fibromyalgia is common in non-Hispanic white adult index patients with primary immunodeficiency, especially women. Chronic fatigue, Sjögren’s syndrome, and IC are significantly associated with fibromyalgia after adjustment for other independent variables.

PMID: 28422000 [PubMed – as supplied by publisher]

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Intravenous immunoglobulin: a biological corticosteroid-sparing agent in some autoimmune conditions.

Lupus. 2017 Jan 01;:961203317696589

Authors: Watad A, Amital H, Shoenfeld Y

Abstract
Intravenous immunoglobulin (IVIg) is increasingly used for the treatment of autoimmune and systemic inflammatory diseases. This compound is effective in a wide range of clinical conditions other than primary immunodeficiency, including autoimmune diseases, inflammatory disorders, infections, organ transplantation, and possibly supportive therapy for cancer. Systemic corticosteroids remain the gold standard treatment for many autoimmune diseases, but their long-term use is associated with complications in diverse organs and systems. Osteoporosis, osteonecrosis, cardiovascular disease, infections, and cancer have been associated with this treatment. Therefore, physicians are occasionally forced to withdraw the treatment with steroids. Biological agents may represent a good alternative, but in addition to being very expensive, these agents may have serious side effects. This review aimed to cover the major advances in the use of IVIg as a steroid-sparing agent in some relevant autoimmune diseases.

PMID: 28420062 [PubMed – as supplied by publisher]

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Immune Serum From Sabin Inactivated Poliovirus Vaccine Immunization Neutralizes Multiple Individual Wild and Vaccine-Derived Polioviruses.

Clin Infect Dis. 2017 Apr 13;:

Authors: Sun M, Li C, Xu W, Liao G, Li R, Zhou J, Li Y, Cai W, Yan D, Che Y, Ying Z, Wang J, Yang H, Ma Y, Ma L, Ji G, Shi L, Jiang S, Li Q

Abstract
Background.: A Sabin strain-based inactivated poliomyelitis vaccine (Sabin-IPV) is the rational option for completely eradicating poliovirus transmission. The neutralizing capacity of Sabin-IPV immune serum to different strains of poliovirus is a key indicator of the clinical protective efficacy of this vaccine.
Methods.: Sera collected from 500 infants enrolled in a randomized, blinded, positive control, phase 2 clinical trial were randomly divided into 5 groups: Groups A, B, and C received high, medium, and low doses, respectively, of Sabin-IPV, while groups D and E received trivalent oral polio vaccine and Salk strain-based IPV, respectively, all on the same schedule. Immune sera were collected after the third dose of primary immunization, and tested in cross-neutralization assays against 19 poliovirus strains of all 3 types.
Results.: All immune sera from all 5 groups interacted with the 19 poliovirus strains with various titers and in a dose-dependent manner. One type 2 immunodeficiency-associated vaccine-derived poliovirus strain was not recognized by these immune sera.
Conclusions.: Sabin-IPV vaccine can induce protective antibodies against currently circulating and reference wild poliovirus strains and most vaccine-derived poliovirus strains, with rare exceptions.

PMID: 28419204 [PubMed – as supplied by publisher]

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Novel PIK3CD mutations affecting N-terminal residues of p110δ cause APDS1 in humans.

J Allergy Clin Immunol. 2017 Apr 13;:

Authors: Takeda AJ, Zhang Y, Dornan GL, Siempelkamp BD, Jenkins ML, Matthews HF, McElwee JJ, Bi W, Seeborg FO, Su HC, Burke JE, Lucas CL

Abstract
APDS is a newly described and prevalent primary immunodeficiency disease, and we now expand the list of mutation sites to include E81K and G124D of p110δ and uncover an intramolecular mechanism of activation that is inhibited by clinically relevant targeting of p110δ.

PMID: 28414062 [PubMed – as supplied by publisher]

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C2 Primary leiomyoma in an immunocompetent woman: A case report and review of literature.

Asian J Neurosurg. 2017 Jan-Mar;12(1):134-138

Authors: Patibandla MR, Nayak MT, Purohit AK, Uppin M, Challa S, Addagada GC, Nukavarapu M

Abstract
Clinical case report and review of the literature. This is the first case of primary leiomyoma in an immunocompetent woman without previous history of uterine leiomyoma being reported in the literature to the best of our knowledge. Leiomyoma, a type of smooth muscle cell tumor, involving the vertebra is extremely rare. There were very few primary leiomyoma in patients with AIDS or in the immune-suppressed patients. This 48-year-old female came with H/o neck pain, weakness and bladder retention. On examination, tone increased in all four limbs, power on the right side of the limbs 4/5, power on the left upper limb 0/5, lower limb 3/5, left plantar was up going, decreased sensation over the left second cervical vertebra (C2) dermatome and all modalities decreased below C2. X-ray and magnetic resonance imaging (MRI) of the cervical spine showed kyphosis of the cervical spine with destruction of the C2 vertebral body along with pathological fracture. The patient underwent decompression of the C2 lesion through the C2 right pedicle with occipito-C1-C3 lateral mass screws fixation. Lesion anterior to the cord was reached by a transpedicular approach and decompression was performed. The lesion was pinkish grey, firm and moderately vascular and was destroying the C2 vertebral body. The patient improved symptomatically in power in the left upper limb and lower limb over the next 1 week duration from 0/5 to 4+/5. Histopathology revealed primary leiomyoma. The patient was evaluated with ultrasound abdomen and contrast tomogram of the chest, abdomen and pelvis to rule out other possible lesions in the lung, intestines and uterus. We suggest that leiomyoma should be included in the differential diagnosis of destructive lytic lesions involving the C2 vertebra. Histopathological examination with immunohistochemistry is necessary for the definitive diagnosis. Treatment of choice is surgery with complete removal.

PMID: 28413557 [PubMed]

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Epidemiology and pathophysiology of malignancy in common variable immunodeficiency?

Allergol Immunopathol (Madr). 2017 Apr 12;:

Authors: Tak Manesh A, Azizi G, Heydari A, Kiaee F, Shaghaghi M, Hossein-Khannazer N, Yazdani R, Abolhassani H, Aghamohammadi A

Abstract
Common variable immunodeficiency (CVID) is a diagnostic category of primary immunodeficiency (PID) which may present with heterogeneous disorders including recurrent infections, autoimmunity, granulomatous diseases, lymphoid and other types of malignancies. Generally, the incidence of malignancy in CVID patients is around 1.5-20.7% and usually occurs during the 4th-6th decade of life. Non-Hodgkin lymphoma is the most frequent malignancy, followed by epithelial tumours of stomach, breast, bladder and cervix. The exact pathological mechanisms for cancer development in CVID are not fully determined; however, several mechanisms including impaired genetic stability, genetic predisposition, immune dysregulation, impaired clearance of oncogenic viruses and bacterial infections, and iatrogenic causes have been proposed to contribute to the high susceptibility of these patients to malignancies.

PMID: 28411962 [PubMed – as supplied by publisher]

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