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Immunopathology & Immunotherapy
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Latest advances in immunopathology diagnosis and treatment
Curated by
Alfredo Corell
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‘Next-generation’ antibodies could complement current therapies.
Alfredo Corell's insight:
Two papers published online today in Nature1, 2 report the impact of antibody therapy on an HIV-related virus that is capable of infecting monkeys and was engineered to carry key portions of the genome of the human virus. Levels of that modified virus, called SHIV, plummeted after the macaques were infused with human antibodies isolated from HIV patients and selected for their potency against a broad array of HIV viruses. Barouch, D. H. et al. Nature doi:10.1038/nature12744 (2013). Shingai, M. et al. Nature doi:10.1038/nature12746 (2013). 
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RT @TeamMEDiary: CD8+ T-Cell Deficiency, Epstein-Barr Infection, Vitamin D Deficiency, and Steps to Autoimmunity: A Unifying Hypothesis
Alfredo Corell's insight:
Autoimmune Dis. 2012; 2012: 189096. Published online 2012 January 24. doi: 10.1155/2012/189096PMCID: PMC3270541CD8+ T-Cell Deficiency, Epstein-Barr Virus Infection, Vitamin D Deficiency, and Steps to Autoimmunity: A Unifying HypothesisMichael P. Pender ConclusionsCD8+ T-cell deficiency is a general feature of chronic autoimmune diseases and also occurs in healthy blood relatives of patients with these diseases. It is proposed that this deficiency is genetically determined and underlies the development of chronic autoimmune diseases by impairing CD8+ T-cell control of EBV infection, with the result that EBV-infected autoreactive B cells accumulate in the target organ where they produce pathogenic autoantibodies and provide costimulatory survival signals to autoreactive T cells. Autoimmunity is postulated to evolve in a series of steps culminating in the development of ectopic lymphoid follicles containing EBV-infected autoreactive B cells in the target organ. It is also proposed that deprivation of sunlight and vitamin D facilitates the development of autoimmune diseases by aggravating the CD8+ T cell deficiency and thereby further impairing control of EBV. The hypothesis makes predictions which can be tested, including the prevention and successful treatment of chronic autoimmune diseases by controlling EBV infection.
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Immunodeficiency and Frequent or Recurrent Infections http://t.co/5ZnsCKGr... Immunodeficiency and Frequent or Recurrent Infections Editor: V. Dimov, M.D., Allergist/Immunologist and Assistant Professor at University of Chicago
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Images in Clinical Medicine from The New England Journal of Medicine — Disfiguring Angioedema A 54-year-old woman presented to our clinic with progressive swelling of her face. (Panel A shows the patient's face without swelling and Panels B through D show two different episodes of swelling, Via Gilbert C FAURE
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There are several activitis on this Primary Immune Deficiency (Hereditary Angioedema, a c1 inhibitor deficiency)
Hereditary angioedema is a rare, but potentially fatal disease. The last 5 years has seen a revolution in the care and treatment of hereditary angioedema.
Alfredo Corell's comment,
September 3, 2013 2:18 PM
But you can sign for a free account, easy to use
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Moderator: Craig B. Langman, MD Northwestern University Head, Dividion of Kidney Diseases Ann and Robert H. Lurie Childern's Hospital Chicago, Illinois
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*Director de Investigación de la Unidad de VIH del Hospital La Paz, Madrid, España.
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immunodeficiency database... De un modo muy intuitivo ayuda en el diagnóstico de las Inmunodeficiencias Primarias y remite a laboratorios de referencia (principalmente americanos) para su diagnóstico.
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Researchers have deployed a potential new weapon against HIV – a combination therapy that targets HIV-infected cells that standard therapies cannot kill.
Alfredo Corell's insight:
Author Summary
Antiretroviral therapy (ART) improves the quality of life for HIV infected individuals. However, ART is currently a lifelong commitment because HIV persists during treatment despite being suppressed below detection. If therapy is stopped, the HIV reappears. A concerted effort is ongoing to develop new eradication therapies to prevent virus rebound, but there are challenges to be overcome. Our work is a major step forward in this process. We measured persistent HIV throughout the body during ART using bone marrow/liver/thymus (BLT) humanized mice, a model validated to study HIV persistence. HIV infected BLT mice were treated with tenofovir, emtricitabine and raltegravir. Despite documented tissue penetration by these drugs, we found that HIV expression persists in cells isolated from all the tissues analyzed (bone marrow, thymus, spleen, lymph nodes, liver, lung, intestines and peripheral blood cells). We therefore complemented ART with an immunotoxin that specifically kills HIV expressing cells while leaving other cells untouched. Our results demonstrate a dramatic reduction in persistent HIV throughout the body resulting from the killing of virus producing cells. Thus, our study provides new insights into the locations of HIV persistence during ART and a demonstration that persistent HIV can be successfully targeted inside the body. Link to PLOs journal: http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1003872
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RT @RIRDF: NIH Scientists Identify a New Immunodeficiency Disease http://t.co/CP96Q4OVcI
Alfredo Corell's insight:
Link to the Nature Immunology Paper: http://www.nature.com/ni/journal/vaop/ncurrent/full/ni.2771.html ;
The study has identified a novel immunodeficiency disease called PASLI, its underlying genetic cause, and a promising, targeted treatment that is already FDA-approved for other purposes. The discovery of PASLI disease also contributes to our understanding of the immune system and highlights the role of PI3K-p110 delta and mTOR in immunity.
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Jennifer W. Leiding, MD,Steven M. Holland, MD Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md Received 23 March 2012; received in revised form 6 June 2012; accepted 25 July 2012. published online 02 October 2012.
Infection with human papillomavirus (HPV) is almost universal and eventually asymptomatic, but pathologic infection with HPV is severe, recurrent, and recalcitrant to therapy. It is also an underappreciated manifestation of primary immunodeficiency. Mutations in EVER1, EVER2, GATA2, CXCR4, and dedicator of cytokinesis 8 (DOCK8) are typically associated with extensive HPV infections, whereas several other primary immune defects result in severe HPV much less frequently. We review immunodeficiencies with severe HPV infections and the mechanisms underlying them.
pdf article: http://download.journals.elsevierhealth.com/pdfs/journals/0091-6749/PIIS0091674912012973.pdf
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Images in Clinical Medicine from The New England Journal of Medicine — Chronic Granulomatous Disease... A 12-year-old boy was admitted to the hospital because of fever, chills, sweats, productive cough, nausea, and vomiting. He had been subject to recurrent pneumonias since the age of 5 years.
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Paolo Sfrisoa, , ,Francesco Casoa,Sofia Tognonb,Paola Galozzia,Alessandra Gavaa,Leonardo Punzia a Rheumatology Unit, Department of Medicine, University of Padova, Padova, Italyb Ophthalmology Unit, Department of Neurosciences, University of Padova, Padova, Italy http://dx.doi.org/10.1016/j.autrev.2012.07.028,
Blau syndrome (BS) is a rare autosomal dominant, autoinflammatory syndrome characterized by the clinical triad of granulomatous recurrent uveitis, dermatitis and symmetric arthritis. The gene responsible for BS has been identified in the caspase recruitment domain gene CARD15/NOD2. In the majority of patients, the disease is characterized by early onset, usually before 3–4 years of age. The manifestations at disease onset are usually represented by articular and cutaneous involvement signs, generally followed later by ocular manifestations which are often the most relevant morbidity of BS. In some cases the presence of fever is also observed; atypical cases of BS have been reported with cardiovascular, neurological, renal, intestinal and other organ involvement. The rarity and the variations in the severity and evolution of its expressions do not permit sufficient data about optimal treatment for patients with BS. The first step of therapy is represented by the use of corticosteroids and successively, in case of unsatisfactory response, by additional treatment with immunosuppressive agents. The results with biologic anti-cytokine agents, such as anti-TNFα and anti-IL1β, are different, particularly with regard to ocular morbidity. Clinical and genetic aspects of the familial and the sporadic form of BS will be discussed and focused on. A description of a case study of an Italian family is also included. Blau syndrome, clinical and genetic aspects http://t.co/BALw5P69...
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A newly identified mutation in the HEATR2 gene causes a rare disease, primary ciliary dyskinesia, in some patients. The gene makes a protein that powers hair-like structures called cilia to beat, removing pollutants and bacteria from the lungs, nose and ears. In cells lining the nose, the HEATR2 protein (red, at left) is present in a healthy person. But in a patient with the disorder, HEATR2 is missing and cilia (green) can’t beat, leading to chronic infections.
Original Publication Horani, A, Druley TE, Bayly PV, Brody SL, Dutcher SK, Ferkol TW et al. Whole-exome capture and sequencing identifies HEATR2 Mutation as a Cause of Primary Ciliary Dyskinesia. American Journal of Human Genetics. Oct. 5, 2012. http://www.cell.com/AJHG/current
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A new study conducted in Japan supports the previously demonstrated safety and efficacy of Hizentra® (Immune Globulin Subcutaneous [Human]) for the treatment of primary immunodeficiency (PID). The data were presented today at the 15th Biennial Meeting of the European Society for Immunodeficiencies (ESID). Hizentra is the first and only 20 percent subcutaneous immunoglobulin (SCIg) therapy in the world for the treatment of PID, a rare and serious group of diseases of the immune system. It is the first-ever SCIg therapy to demonstrate safety and efficacy in Japanese subjects. Based on these excellent results, CSL Behring submitted the new drug application (NDA) for Hizentra to the Pharmaceutical and Medicines Devices Agency (PMDA) in Japan on 28 September, 2012
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IDbases are locus-specific databases for immunodeficiency-causing mutations. They establish database for every immunodeficiency or provide links to those maintained elsewhere.
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Given the limitations of antiretroviral therapy and recent advances in our understanding of HIV persistence during effective treatment, there is a growing recognition that a cure for HIV infection is both needed and feasible. The International AIDS Society convened a group of international experts to develop a scientific strategy for research towards an HIV cure. Several priorities for basic, translational and clinical research were identified. This Opinion article summarizes the group's recommended key goals for the international community.
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Btk is the protein affected in XLA, a disease identified as a B cell differentiation defect. Btk is crucial for B cell differentiation and activation, but its role in other cells is not fully understood. This review focuses on the function of Btk in monocytes, neutrophils, and platelets and the receptors and signaling cascades in such cells with which Btk is associated.