Manish Butte

Precision Therapy for the Treatment of Primary Immunodysregulatory Diseases.

Immunol Allergy Clin North Am. 2020 Aug;40(3):511-526

Authors: Chellapandian D, Chitty-Lopez M, Leiding JW

Abstract
Precision therapy is a concept in which medical treatment is tailored to the patient’s individual needs based on individual characteristics and mechanism of disease. Primary immunodysregulatory disorders are an expanding group of primary immunodeficiency diseases that are characterized by early onset autoimmunity and autoinflammation. Precision therapy allows for the alteration of the aberrant immune response leading to clinical improvement of disease related manifestations. This article reviews targeted precision-based therapy for treatment of cytotoxic T-lymphocyte antigen haploinsufficiency, lipopolysaccharide-responsive beige-like anchor deficiency, activated PI3K deficiency syndrome, signal transducer and activator of transcription- 1 and -3 – gain-of-function disorders, and disorders of inflammasome activation.

PMID: 32654696 [PubMed – in process]

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Diagnosis and management of Specific Antibody Deficiency.

Immunol Allergy Clin North Am. 2020 Aug;40(3):499-510

Authors: Perez EE, Ballow M

Abstract
Specific antibody deficiency is a primary immunodeficiency disease recognized by the International Union of Immunology Societies and defined by recurrent respiratory infections with normal immunoglobulins, but diminished antibody responses to polysaccharide antigens after vaccination with the 23 valent pneumococcal polysaccharide vaccine. Clinical immunologists struggle with diagnosis and treatment, because the definition of an adequate response to immunization remains controversial. Specific antibody deficiency is managed clinically with close follow-up and prompt treatment of infections, antibiotic prophylaxis, or immune globulin therapy. Treatment is individualized using clinical judgment and existing practice guidelines, which will likely evolve as more studies become available.

PMID: 32654695 [PubMed – in process]

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Hemophagocytic Lymphohistiocytosis: Lessons Learned from the Dark Side.

Immunol Allergy Clin North Am. 2020 Aug;40(3):485-497

Authors: Chellapandian D

Abstract
Hemophagocytic lymphohistiocytosis (HLH) is a rare but severe form of immune dysregulation often presenting as unremitting fever, cytopenia, hepatosplenomegaly, coagulopathy, and elevation of typical HLH biomarkers. HLH is universally fatal, if left untreated. The HLH-2004 criteria are widely used to diagnose this condition, but there is growing concerns across different settings that its application may result in undertreatment of certain patients. There is an expanding spectrum of genetic conditions that can be complicated by HLH. This review summarizes the current concepts in HLH, the lessons learned from the past, and provide an overview of the latest diagnostic and treatment modalities.

PMID: 32654694 [PubMed – in process]

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IKAROS Family Zinc Finger 1-Associated Diseases in Primary Immunodeficiency Patients.

Immunol Allergy Clin North Am. 2020 Aug;40(3):461-470

Authors: Nunes-Santos CJ, Kuehn HS, Rosenzweig SD

Abstract
Ikaros zinc finger 1 (IKZF1 or Ikaros) is a hematopoietic zinc finger DNA-binding transcription factor that acts as a critical regulator of lymphocyte and myeloid differentiation. Loss-of-function germline heterozygous mutations in IKZF1 affecting DNA-binding were described as causative of 2 distinct primary immunodeficiency (PID)/inborn error of immunity diseases. Mutations acting by haploinsufficiency present with a common variable immune deficiency-like phenotype mainly characterized by increased susceptibility to infections. Mutations acting in a dominant negative fashion present with a combined immunodeficiency phenotype with high prevalence of Pneumocystis jirovecii pneumonia. Pathophysiology and manifestations of IKAROS-associated diseases in patients with PID are reviewed here.

PMID: 32654692 [PubMed – in process]

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Chronic Lung Disease in Primary Antibody Deficiency: Diagnosis and Management.

Immunol Allergy Clin North Am. 2020 Aug;40(3):437-459

Authors: Maglione PJ

Abstract
Chronic lung disease is a complication of primary antibody deficiency (PAD) associated with significant morbidity and mortality. Manifestations of lung disease in PAD are numerous. Thoughtful application of diagnostic approaches is imperative to accurately identify the form of disease. Much of the treatment used is adapted from immunocompetent populations. Recent genomic and translational medicine advances have led to specific treatments. As chronic lung disease has continued to affect patients with PAD, we hope that continued advancements in our understanding of pulmonary pathology will ultimately lead to effective methods that alleviate impact on quality of life and survival.

PMID: 32654691 [PubMed – in process]

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Vaccines in Patients with Primary Immune Deficiency.

Immunol Allergy Clin North Am. 2020 Aug;40(3):421-435

Authors: Bonilla FA

Abstract
Evaluation of antibodies produced after immunization is central to immune deficiency diagnosis. This includes assessment of responses to routine immunizations as well as to vaccines administered specifically for diagnosis. Here, we present the basic concepts of the humoral immune response and their relevance for vaccine composition and diagnosis of immune deficiency. Current vaccines are discussed, including nonviable protein and glycoprotein vaccines, pure polysaccharide vaccines, polysaccharide-protein conjugate vaccines, and live agent vaccines. Diagnostic and therapeutic applications of vaccine antibody measurement are discussed in depth. Important adverse effects of vaccines are also presented.

PMID: 32654690 [PubMed – in process]

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Defining Common Variable Immunodeficiency Disorders in 2020.

Immunol Allergy Clin North Am. 2020 Aug;40(3):403-420

Authors: Ameratunga R, Allan C, Woon ST

Abstract
Common variable immunodeficiency disorders (CVID) are the most frequent symptomatic primary immune deficiency in adults. Because there is no known cause for these conditions, there is no single clinical feature or laboratory test that can confirm the diagnosis with certainty. If a causative mutation is identified, patients are deemed to have a CVID-like disorder caused by a specific primary immunodeficiency/inborn error of immunity. In the remaining patients, the explanation for these disorders remains unclear. The understanding of CVID continues to evolve and the authors review recent studies, which have addressed some of these uncertainties.

PMID: 32654689 [PubMed – in process]

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The Importance of Primary Immune Deficiency Registries: The United States Immunodeficiency Network Registry.

Immunol Allergy Clin North Am. 2020 Aug;40(3):385-402

Authors: Lopes JP, Cunningham-Rundles C

Abstract
The importance of registries is vital for almost every human disease but crucial for rare disorders, where the centralized collection, organization, and quality check of data create a platform from where multiple analyses and scientific advances are possible. In this article, the authors review the creation of the United States Immunodeficiency Network registry, its role, and the numerous scientific achievements generated from the collective effort of many.

PMID: 32654688 [PubMed – in process]

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