Manish Butte

PROMIDISα: a TCRα signature associated with immunodeficiencies caused by V(D)J recombination defects.

June 16, 2018 By Manish Butte

PROMIDISα: a TCRα signature associated with immunodeficiencies caused by V(D)J recombination defects.

J Allergy Clin Immunol. 2018 Jun 12;:

Authors: Berland A, Rosain J, Kaltenbach S, Allain V, Mahlaoui N, Melki I, Fievet A, Dubois d’Enghien C, Ouachée-Chardin M, Perrin L, Auger N, Cipe FE, Finocchi A, Dogu F, Suarez F, Moshous D, Leblanc T, Belot A, Fieschi C, Boutboul D, Malphettes M, Galicier L, Oksenhendler E, Blanche S, Fischer A, Revy P, Stoppa-Lyonnet D, Picard C, de Villartay JP

Abstract
– BACKGROUND: V(D)J recombination ensures the diversity of the adaptive immune system. While its complete defect causes Severe Combined Immunodeficiency (T-B-SCID), its suboptimal activity, is associated with a broad spectrum of immune manifestations such as late onset combined immunodeficiency and autoimmunity. The earliest molecular diagnosis of these patients is required to adopt the best therapy strategy, in particular when it involves myelo-ablative conditioning regimen for hematopoietic stem cell transplantation (HSCT).
– OBJECTIVE: We aimed at developing biomarkers based on the analysis of TCRα repertoire to assist in the diagnosis of primary immunodeficient patients (PID) with V(D)J recombination and DNA repair deficiencies.
– METHODS: We used flow cytometry (FACS) analysis to quantify TCR-Vα7.2 expressing T lymphocytes in peripheral blood and developed PROMIDISα, a multiplex RT-PCR/NGS assay, to evaluate a subset of the TCRα repertoire in T lymphocytes.
– RESULTS: The combined FACS and PROMIDISα analyses revealed specific signatures in patients with V(D)J recombination defective PIDs or Ataxia telangiectasia/Nijmegen breakage syndromes (AT/NBS).
– CONCLUSION: Analysis of the TCRα repertoire is particularly appropriate, in a prospective way, to identify patients with partial immune defects caused by suboptimal V(D)J recombination activity and/or DNA repair defect. It also constitutes a valuable tool for the retrospective in vivo functional validation of variants identified through exome or panel sequencing. Its broader implementation may be of interest to assist early diagnosis of patients presenting with hypomorphic DNA repair defects inclined to develop acute toxicity during pre-HSCT conditioning.

PMID: 29906526 [PubMed – as supplied by publisher]

[Percutaneous nephrolithotripsy in a patient with primary immunodeficiency (a case report)].

June 15, 2018 By Manish Butte

[Percutaneous nephrolithotripsy in a patient with primary immunodeficiency (a case report)].

Urologiia. 2018 May;(2):104-107

Authors: Kozachikhina SI, Martov AG, Dutov SV, Andronov AS, Yarovoi SK, Dzhalilov OV

Abstract
This article presents a case study of a female patient with primary immunodeficiency, who underwent percutaneous nephrolithotripsy. The presence of a serious concomitant disease affects different aspects of preoperative and postoperative management of the patient. The choice of percutaneous nephrolithotripsy is necessitated by the need to render the patient stone free using a one-stage and the most effective surgical modality. The article describes the choice of antibacterial therapy to treat inflammatory complications in this category of patients. Broad-spectrum antibiotics should be used to prevent the onset of pyelonephritis, while pyelonephritis exacerbation requires administration of reserve antibiotics in combination with human immunoglobulin.

PMID: 29901303 [PubMed – in process]

Macrophage activation syndrome associated with griscelli syndrome type 2: case report and review of literature.

June 15, 2018 By Manish Butte

Macrophage activation syndrome associated with griscelli syndrome type 2: case report and review of literature.

Pan Afr Med J. 2018;29:75

Authors: Sefsafi Z, Hasbaoui BE, Kili A, Agadr A, Khattab M

Abstract
Macrophage activation syndrome (MAS) is a severe and potentially fatal life-threatening condition associated with excessive activation and expansion of T cells with macrophages and a high expression of cytokines, resulting in an uncontrolled inflammatory response, with high levels of macrophage colony-stimulating factor and causing multiorgan damage. This syndrome is classified into primary (genetic/familial) or secondary forms to several etiologies, such as infections, neoplasias mainly hemopathies or autoimmune diseases. It is characterised clinically by unremitting high fever, pancytopaenia, hepatosplenomegaly, hepatic dysfunction, encephalopathy, coagulation abnormalities and sharply increased levels of ferritin. The pathognomonic feature of the syndrome is seen on bone marrow examination, which frequently, though not always, reveals numerous morphologically benign macrophages exhibiting haemophagocytic activity. Because MAS can follow a rapidly fatal course, prompt recognition of its clinical and laboratory features and immediate therapeutic intervention are essential. However, it is difficult to distinguish underlying disease flare, infectious complications or medication side effects from MAS. Although, the pathogenesis of MAS is unclear, the hallmark of the syndrome is an uncontrolled activation and proliferation of T lymphocytes and macrophages, leading to massive hypersecretion of pro-inflammatory cytokines. Mutations in cytolytic pathway genes are increasingly being recognised in children who develop MAS in his secondary form. We present here a case of Macrophage activation syndrome associated with Griscelli syndrome type 2 in a 3-years-old boy who had been referred due to severe sepsis with non-remitting high fever, generalized lymphoadenopathy and hepato-splenomegaly. Laboratory data revealed pancytopenia with high concentrations of triglycerides, ferritin and lactic dehydrogenase while the bone marrow revealed numerous morphologically benign macrophages with haemophagocytic activity that comforting the diagnosis of a SAM according to Ravelli and HLH-2004 criteria. Griscelli syndrome (GS) was evoked on; consanguineous family, recurrent infection, very light silvery-gray color of the hair and eyebrows, Light microscopy examination of the hair showed large, irregular clumps of pigments characteristic of GS. The molecular biology showed mutation in RAB27A gene confirming the diagnosis of a Griscelli syndrome type 2. The first-line therapy was based on the parenteral administration of high doses of corticosteroids, associated with immunosuppressive drugs, cyclosporine A and etoposide waiting for bone marrow transplantation (BMT).

PMID: 29875956 [PubMed – indexed for MEDLINE]

Immunoglobulin replacement therapy in primary and secondary antibody deficiency: The correct clinical approach.

June 13, 2018 By Manish Butte

Immunoglobulin replacement therapy in primary and secondary antibody deficiency: The correct clinical approach.

Int Immunopharmacol. 2017 Nov;52:136-142

Authors: Pecoraro A, Crescenzi L, Granata F, Genovese A, Spadaro G

Abstract
Immunoglobulin therapy is the administration of human polyvalent IgG and represents the most effective treatment to prevent recurrent infections in antibody deficiency patients. Primary antibody deficiency represents the main indication of immunoglobulin replacement therapy and includes a wide range of disorders characterized by impaired antibody production in response to pathogens and recurrent infections. However, not all primary antibody deficiency patients require immunoglobulin replacement. Indeed, immunoglobulin preparations are expensive and, once prescribed, usually result in lifelong therapy. Moreover, many patients significantly benefit from a long-term antibiotic prophylaxis and a prompt begin of antibiotic therapy in case of infectious events. Even more controversial is the decision to initiate immunoglobulin replacement therapy in secondary antibody deficiency, a heterogeneous and expanding group including B-cell lymphoproliferative syndromes, protein losing states and therapeutic agents. This review seeks to define the indication to immunoglobulin replacement in primary and secondary antibody deficiency disorders, distinguishing those in which the beginning of immunoglobulin therapy is always indicated at the same time as the diagnosis has been made, from those lacking of defined indication to replacement therapy. In addition, we propose a clinical approach, mainly based on the evaluation of infectious history, vaccine response and bronchiectasis finding, to support the decision to initiate immunoglobulin therapy in an individual patient.

PMID: 28898770 [PubMed – indexed for MEDLINE]

The Utility of Next-Generation Sequencing for Primary Immunodeficiency Disorders: Experience from a Clinical Diagnostic Laboratory.

June 12, 2018 By Manish Butte

The Utility of Next-Generation Sequencing for Primary Immunodeficiency Disorders: Experience from a Clinical Diagnostic Laboratory.

Biomed Res Int. 2018;2018:9647253

Authors: Bisgin A, Boga I, Yilmaz M, Bingol G, Altintas D

Abstract
Introduction: Primary immune deficiency disorders (PIDs) are a group of diseases with profound defects in immune cells. The traditional diagnostics have evolved from clinical evaluation, flow cytometry, western blotting, and Sanger sequencing to focusing on small groups of genes. However, this is not sufficient to confirm the suspicion of certain PIDs. Our innovative approach to diagnostics outlines the algorithm for PIDs and the clinical utility of immunophenotyping with a custom-designed multigene panel.
Materials and Methods: We have designed a diagnostic algorithm based on flow cytometry studies to classify the patients; then the selected multigene panel was sequenced. In silico analysis for mutations was carried out using SIFT, Polyphen-2, and MutationTaster.
Results and Discussion: The causative mutation was identified in 46% of PIDs. Based on these results, this new algorithm including immune phenotyping and NGS for PIDs was suggested for the clinical use.
Conclusions: This study provides a thorough validation of diagnostic algorithm and indicates that still the traditional methods can be used to collect significant information related to design of most current diagnostics. The benefits of such testing are for diagnosis and prevention including the prenatal and preimplantation diagnosis, prognosis, treatment, and research.

PMID: 29888287 [PubMed – in process]

Hematopoietic stem cell transplantation for cytidine triphosphate synthase 1 (CTPS1) deficiency.

June 10, 2018 By Manish Butte

Hematopoietic stem cell transplantation for cytidine triphosphate synthase 1 (CTPS1) deficiency.

Bone Marrow Transplant. 2018 Jun 08;:

Authors: Nademi Z, Wynn RF, Slatter M, Hughes SM, Bonney D, Qasim W, Latour S, Trück J, Patel S, Abinun M, Flood T, Hambleton S, Cant AJ, Gennery AR, Arkwright PD

PMID: 29884857 [PubMed – as supplied by publisher]

Infectious flexor hand tenosynovitis: State of knowledge. A study of 120 cases.

June 9, 2018 By Manish Butte

Infectious flexor hand tenosynovitis: State of knowledge. A study of 120 cases.

J Orthop. 2018 Jun;15(2):701-706

Authors: Mamane W, Lippmann S, Israel D, Ramdhian-Wihlm R, Temam M, Mas V, Pierrart J, Masmejean EH

Abstract
Introduction: Since Kanavel in 1905, knowledge of phlegmon of flexor tendon sheaths of the fingers have evolved over the twentieth century. This serious infection is 20% of infections of the hand and may have adverse consequences for the function of the finger and even beyond, of the hand. Amputation is always a risk. Frequently face this type of infection, we conducted a retrospective study and made an inventory of knowledge in order to consolidate and improve the overall care.
Materials & Methods: The study was retrospective and cross, focused on 120 patients operated on at Hand Surgery Unit, during 4 years. Inclusion criteria were primary or secondary infection of the sheath of the flexor tendons of the fingers.The evaluation focused on clinical and paraclinical perioperative parameters. At last follow, digital mobility (Total Active Motion), the functional score of QuickDASH and the socio-professional consequences were evaluated.
Results: The mean age was 40 years, with a male predominance. The hospital stay was 17 days on average (3 days to 80 days). From the classification of Michon, as amended by Sokolow, we found 60 Stage I, 48 stage II, 12 stage III. The Total Active Motion was respectively 240 °, 140 °, 40 °. QuickDASH scores were respectively 20, 56 and 90 out of 100. The time for return to work was 1 month for stage I, 4 months for stage II and 12 months for stage III.
Discussion: The long-term functional outcome was generally poor, with stiffness or digital amputation. The poor prognostic factors were: the initial advanced stage of infection, infection beta-haemolytic Streptococcus group A, and delayed surgical management. Smoking was identified as a new risk factor in this disease, as well as diabetes or immunodeficiency. This study confirmed the predominance of Staphylococcus, and scalability of the infection depending on the mode of contamination, and / or type of germ that is to say, scalability schedule for β-hemolytic streptococci group A chronic and scalability for intracellular bacteria (mycobacteria).
Conclusion: Any suspicion of flexor hand tenosynovitis should lead to an emergency surgical exploration, not primary antibiotics prescription!

PMID: 29881224 [PubMed]

The United Kingdom Primary Immune Deficiency (UKPID) registry 2012 to 2017.

June 8, 2018 By Manish Butte

The United Kingdom Primary Immune Deficiency (UKPID) registry 2012 to 2017.

Clin Exp Immunol. 2018 Jun;192(3):284-291

Authors: Shillitoe B, Bangs C, Guzman D, Gennery AR, Longhurst HJ, Slatter M, Edgar DM, Thomas M, Worth A, Huissoon A, Arkwright PD, Jolles S, Bourne H, Alachkar H, Savic S, Kumararatne DS, Patel S, Baxendale H, Noorani S, Yong PFK, Waruiru C, Pavaladurai V, Kelleher P, Herriot R, Bernatonienne J, Bhole M, Steele C, Hayman G, Richter A, Gompels M, Chopra C, Garcez T, Buckland M

Abstract
This is the second report of the United Kingdom Primary Immunodeficiency (UKPID) registry. The registry will be a decade old in 2018 and, as of August 2017, had recruited 4758 patients encompassing 97% of immunology centres within the United Kingdom. This represents a doubling of recruitment into the registry since we reported on 2229 patients included in our first report of 2013. Minimum PID prevalence in the United Kingdom is currently 5·90/100 000 and an average incidence of PID between 1980 and 2000 of 7·6 cases per 100 000 UK live births. Data are presented on the frequency of diseases recorded, disease prevalence, diagnostic delay and treatment modality, including haematopoietic stem cell transplantation (HSCT) and gene therapy. The registry provides valuable information to clinicians, researchers, service commissioners and industry alike on PID within the United Kingdom, which may not otherwise be available without the existence of a well-established registry.

PMID: 29878323 [PubMed – in process]

[Haemophagocytic syndromes: The importance of early diagnosis and treatment].

June 7, 2018 By Manish Butte

[Haemophagocytic syndromes: The importance of early diagnosis and treatment].

An Pediatr (Barc). 2018 Jun 02;:

Authors: Astigarraga I, Gonzalez-Granado LI, Allende LM, Alsina L

Abstract
Haemophagocytic syndrome, or haemophagocytic lymphohistiocytosis (HLH), is a disorder with high mortality, typically recognised at paediatric age. Without proper treatment, HLH can be fatal. The risk of a rapid progression to multi-organ failure and central nervous system involvement leading to long-term sequelae, are the most feared consequences of a diagnostic delay. Therefore, HLH is a medical emergency that paediatricians should be able to identify in a patient with fever and progressive worsening of general condition. The application of the HLH diagnostic criteria, which include clinical and analytical data (as well as a bone marrow aspirate), and the search for a trigger (infectious, oncological, rheumatological, or metabolic). These are decisive for the establishment of a targeted treatment, which aims at neutralising the trigger and reducing the hyper-inflammation. The most relevant data for general paediatricians are presented in this review, including the physiopathology, diagnosis, and treatment of this serious disease.

PMID: 29871839 [PubMed – as supplied by publisher]

Interleukin-2-Inducible T-Cell Kinase Deficiency-New Patients, New Insight?

June 6, 2018 By Manish Butte

Interleukin-2-Inducible T-Cell Kinase Deficiency-New Patients, New Insight?

Front Immunol. 2018;9:979

Authors: Ghosh S, Drexler I, Bhatia S, Gennery AR, Borkhardt A

Abstract
Patients with primary immunodeficiency can be prone to severe Epstein-Barr virus (EBV) associated immune dysregulation. Individuals with mutations in the interleukin-2-inducible T-cell kinase (ITK) gene experience Hodgkin and non-Hodgkin lymphoma, EBV lymphoproliferative disease, hemophagocytic lymphohistiocytosis, and dysgammaglobulinemia. In this review, we give an update on further reported patients. We believe that current clinical data advocate early definitive treatment by hematopoietic stem cell transplantation, as transplant outcome in primary immunodeficiency disorders in general has gradually improved in recent years. Furthermore, we summarize experimental data in the murine model to provide further insight of pathophysiology in ITK deficiency.

PMID: 29867957 [PubMed]