Manish Butte

Initial intravenous immunoglobulin doses should be based on adjusted body weight in obese patients with primary immunodeficiency disorders.

Allergy Asthma Clin Immunol. 2017;13:47

Authors: Ameratunga R

Abstract
Background: Immunoglobulin therapy plays a critical role in the treatment of immunodeficiency disorders as well as autoimmune and inflammatory conditions. In immunodeficient patients, there has been controversy whether initial loading doses of intravenous (IVIG) should be based on actual body weight or a calculated parameter such as adjusted body weight in obese patients.
Case presentation: I describe a patient with Common Variable Immunodeficiency disorder (CVID) who underwent bariatric surgery for morbid obesity. Her weight decreased by 50% to below her calculated ideal body weight (IBW) while her immunoglobulin requirement fell by approximately 20%. Her steady state serum IgG increased from approximately 7 g/l to 11.7 g/l concomitant with weight loss.
Conclusions: I present this observation as support for the recommendation that initial loading doses of SCIG/IVIG in immunodeficiency should be based on adjusted body weight (AjBW) and not actual body weight in obese patients. This has important fiscal implications for treating obese patients with immunodeficiency disorders.

PMID: 29225631 [PubMed]

Powered by WPeMatico

Anti-cytokine autoantibodies in a patient with a heterozygous NFKB2 mutation.

J Allergy Clin Immunol. 2017 Dec 07;:

Authors: Ramakrishnan KA, Rae W, Barcenas-Morales G, Gao Y, Pengelly RJ, Patel SV, Kumararatne DS, Ennis S, Döffinger R, Faust SN, Williams AP

Abstract
We report a family with a heterozygous NFKB2 mutation in which anti-cytokine autoantibodies were identified in one individual. Rituximab therapy for autoantibodies led to a reduction in anti-cytokine autoantibodies and a marked improvement in infectious susceptibility.

PMID: 29225085 [PubMed – as supplied by publisher]

Powered by WPeMatico

Chronic granulomatous disease in children: A single center experience.

Clin Immunol. 2017 Dec 06;:

Authors: Beghin A, Comini M, Soresina A, Imberti L, Zucchi M, Plebani A, Montanelli A, Porta F, Lanfranchi A

Abstract
Chronic Granulomatous Disease (CGD) is caused by the failure of the phagocytes to kill pathogens. We carried out a retrospective analysis of cellular, molecular and clinical features of 14 young patients (mean age at the onset of symptoms and diagnosis: 10 and 25months, respectively), 7 with autosomal recessive and 7 X-linked form, referred to the Children’s Hospital of Brescia between 1999 and 2016. Two new mutations were found, one localized in the CYBB and one in the NCF1 genes. Twelve patients were followed in our institution; the average length of their follow-up after diagnosis was 66months in X-linked patients and 126months in autosomal recessive inheritance. The overall survival was 67%, 40% in X-linked and 86% in autosomal recessive form. Eight patients were treated with HSCT. We did not find a clear correlation between the clinical symptoms and the type of mutation, but the fine characterization of the patients was mandatory for therapeutic option, genetic counseling and prenatal diagnosis.

PMID: 29223406 [PubMed – as supplied by publisher]

Powered by WPeMatico

Immunological Rare Diseases.

Adv Exp Med Biol. 2017;1031:497-509

Authors: Baldovino S, Menegatti E, Roccatello D, Sciascia S

Abstract
The immune system is delegated to defend the body from attacks from outside or inside. Many diseases can affect immune system reducing its ability to defend self or inducing an abnormal response against external or internal antigens. Rare diseases affecting immune system present some issue in common with other rare diseases and some peculiarities due to the huge variability in the disease’s expression. However, a correct estimation of the epidemiology of rare disorders is necessary for evaluating the prognosis and the responses to new therapies, for planning proper public health services, and finally to establish fair and sustainable prices for innovative medicines. Due to the enormous number of different rare immunological diseases, in this chapter we are going to analyse some of them that can be considered paradigmatic of the various expressions of disease.

PMID: 29214588 [PubMed – in process]

Powered by WPeMatico

Approach to a Child with Primary Immunodeficiency Made Simple.

Indian Dermatol Online J. 2017 Nov-Dec;8(6):391-405

Authors: Sharma D, Jindal AK, Rawat A, Singh S

Abstract
Primary immunodeficiency disorders (PIDs) are a group of disorders affecting the capability to fight against infection. These include defects in T cells and B cells affecting cell-mediated and humoral immunity, respectively, combined humoral and cell-mediated immunodeficiency, defects in phagocytosis, complement defects, and defects in cytokine or cytokine signalling pathways which are detrimental for immune function. Depending upon the type and severity, age at onset of symptoms can vary from neonatal period to late childhood. Clinically, this group of disorders can involve any organ system of an individual such as respiratory system, gastrointestinal system, skin and mucous membrane, bone and joints, endocrine organs, and nervous system. Common dermatological manifestations include eczema, warts, molluscum contagiosum, mucocutaneous candidiasis, recurrent nonhealing ulcers, skin abscesses, erythroderma, petechiae, and nail changes. The common skin manifestations of various PIDs include eczema (seen in Wiskott-Aldrich syndrome and autosomal dominant hyper IgE syndrome); erythroderma (in Omen syndrome); viral warts or molluscum contagiosum (in autosomal recessive hyper IgE syndrome); chronic mucocutaneous candidiasis (in hyper IgE syndrome, autoimmune polyendocrinopathy candidiasis ectodermal dysplasia syndrome, Th17 cell defects); recurrent nonhealing ulcers (in leucocyte adhesion defect); skin abscesses (in antibody defects, hyper IgE syndrome, and chronic granulomatous disease); petechial or purpuric spots (in Wiskott-Aldrich syndrome).

PMID: 29204384 [PubMed]

Powered by WPeMatico

Clinical Challenges: Identification of Patients With Novel Primary Immunodeficiency Syndromes.

J Pediatr Hematol Oncol. 2017 Dec 01;:

Authors: Buchbinder D, Seppanen M, Rao VK, Uzel G, Nugent D

Abstract
Novel primary immunodeficiency disorders are being identified with next generation sequencing technologies. We describe 1 patient with cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) haploinsufficiency who had recurrent enhancing brain lesions, nodular pulmonary infiltrates, hepatosplenomegaly, immune cytopenias, as well as progressive hypogammaglobulinemia and lymphopenia. We describe a second patient with activated p110δ syndrome (APDS)/p110δ activating mutation causing senescent T cells, lymphadenopathy, and immunodeficiency (PASLI) in association with recurrent respiratory tract infections, Epstein-Barr virus infection, lymphadenopathy, elevated serum IgM, and progressive lymphopenia. These presentations highlight the need for astute clinical judgment in the evaluation of patients with potential primary immunodeficiency disorders.

PMID: 29200144 [PubMed – as supplied by publisher]

Powered by WPeMatico

Burden of Poor Health Conditions and Quality of Life in 656 Children with Primary Immunodeficiency.

J Pediatr. 2017 Nov 30;:

Authors: Barlogis V, Mahlaoui N, Auquier P, Fouyssac F, Pellier I, Vercasson C, Allouche M, De Azevedo CB, Moshous D, Neven B, Pasquet M, Jeziorski E, Aladjidi N, Thomas C, Gandemer V, Mazingue F, Picard C, Blanche S, Michel G, Fischer A

Abstract
OBJECTIVE: To gain insight into how primary immunodeficiencies (PIDs) affect children’s health status and quality of life.
STUDY DESIGN: The French Reference Center for PIDs conducted a prospective multicenter cohort that enrolled participants who met all criteria: patients included in the French Reference Center for PIDs registry, children younger than18 years, and living in France. Participants were asked to complete both a health questionnaire and a health-related quality of life (HR-QoL) questionnaire. A severity score was assigned to each health condition: grade 1 (mild) to grade 4 (life-threatening). HR-QoL in children was compared with age- and sex-matched French norms.
RESULTS: Among 1047 eligible children, 656 were included in the study, and 117 had undergone hematopoietic stem cell transplantation; 40% experienced at least one grade 4 condition, and 83% experienced at least one grade 3 or 4 condition. Compared with the French norms, children with PID scored significantly lower for most HR-QoL domains. Low HR-QoL scores were associated strongly with burden of poor conditions.
CONCLUSIONS: Our results quantify the magnitude of conditions in children with PID and demonstrate that the deleterious health effects borne by patients already are evident in childhood. These results emphasize the need to closely monitor this vulnerable population and establish multidisciplinary healthcare teams from childhood.
TRIAL REGISTRATION: ClinicalTrials.gov: NCT02868333 and EudraCT 2012-A0033-35.

PMID: 29198545 [PubMed – as supplied by publisher]

Powered by WPeMatico

Outcomes after Allogeneic Transplant in Patients with Wiskott-Aldrich Syndrome.

Biol Blood Marrow Transplant. 2017 Nov 28;:

Authors: Ngwube A, Hanson IC, Orange J, Rider NL, Seeborg F, Shearer W, Noroski L, Nicholas S, Forbes L, Leung K, Sasa G, Naik S, Hegde M, Omer B, Ahmed N, Allen C, Gottschalk S, Wu MF, Liu H, Brenner M, Heslop H, Krance R, Martinez C

Abstract
Wiskott-Aldrich syndrome (WAS) is a rare X-linked disorder characterized by a triad of immunodeficiency, eczema and thrombocytopenia. Currently, hematopoietic stem cell transplant (HSCT) is the most reliable curative treatment with excellent results for patients with HLA-matched family or unrelated donors. However, even after fully myeloablative preparative regimens, mixed donor chimerism is a potential concern. We performed a retrospective chart review of twelve children who underwent allogeneic hematopoietic stem cell transplant for WAS to report our experience. The median age at transplant was 10.5 months (range 3-39 months).The median nucleated cell dose from the marrow was 4.55×109 (0.3- 7.9×109)/kg. The median times to neutrophil and platelet engraftment were 19 (range 13-27) and 18.5 (range 12-31) days respectively. The overall survival is 92% with median follow up of 67 months (range 3-146). Two patients developed grade IV acute graft versus host disease and one died on Day +99. Five of twelve (42%) had mixed donor chimerism, (range: 12-85%) at Day+ 180. None of the pre-transplant patient parameters were predictive of mixed chimerism. Nonetheless, of these 5 patients, 2 had normalization of the platelet count despite the mixed chimerism, 2 had full donor chimerism after receiving a second transplant with the same donor, and 1 remains transfusion dependent awaiting a 2nd transplant. Hence, even with a significant rate of mixed chimerism, HSCT provides substantial benefit to WAS patients, with excellent overall survival.

PMID: 29196075 [PubMed – as supplied by publisher]

Powered by WPeMatico

Clinical indications for intravenous immunoglobulin utilization in a tertiary medical center: a 9-year retrospective study.

Transfusion. 2017 Nov 27;:

Authors: Shemer A, Kivity S, Shoenfeld Y

Abstract
BACKGROUND: Intravenous immunoglobulins (IVIG) are a biologic product originally developed to treat immunocompromised patients. In the past decades, there has been increased utilization of IVIG in autoimmune conditions. The objectives were to evaluate the clinical use of IVIG in the largest tertiary medical center in Israel and to determine top uses, estimate off-label usage, and assess consumption of this blood product.
STUDY DESIGN AND METHODS: We conducted an observational, retrospective study involving all patients who received IVIG from 2007 through 2015. Subjects were classified into five groups according to the indication for treatment.
RESULTS: A total of 1117 patients were identified. The mean (±SD) ages of adults and children were 55 ± 17 and 8 ± 7 years, respectively. Most common indication for treatment were immune-mediated conditions (54%), followed by secondary immunodeficiency (28%), primary immunodeficiency (10%), infections (4%), and miscellaneous (4%). The main immune-mediated conditions treated were hematologic disorders (305 patients, 27%), neurologic disorders (219 patients, 20%), and rheumatologic conditions (79 patients, 7%). Overall, a significant change in study period was observed in the number of patients (p < 0.001), consumption of IVIG (p < 0.01), and amount of IVIG administered per patient (p < 0.01). Fifty-six percent of the IVIG infusions were given for off-label Food and Drug Administration (FDA) indications.
CONCLUSION: In this study, we demonstrated that immune-mediated conditions represent the majority of indications for treatment with IVIG. We observed a 417% increase in IVIG administration (g) over time, attributed mainly to autoimmune diseases. Many indications are still off-label according to FDA recommendations.

PMID: 29193136 [PubMed – as supplied by publisher]

Powered by WPeMatico