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Tuesday, April 2, 2013

The B cell encyclopedia of lung disease



Lung disease researchers could be accused of an excessive focus on aberrant T cell mechanisms in studies of most airway diseases.  In this month’s issue, Kato and co-authors have elegantly restored some balance to this T cell biology-centric perspective [p933-957#].  In what can only be described as an encyclopedic version of a B cell immunology textbook, complete with impressive tables and illustrated figures, Kato et al. deliver the sum of current thinking and knowledge on B cell and plasma cell biology in the respiratory system. [Journal of Allergy and Clinical Immunology 2013;131(4):933-957]

The authors begin with a comprehensive review of adaptive immunity including B lymphocyte development, lineage differentiation and commitment in secondary lymphoid organs [SLO] under the influence of cytokines, class switch recombination, and chemokine-induced trafficking and recirculation.  Kato et al. discusses B cell and plasma cell localization and activation in the airway parenchyma, draining lymph nodes and mucosa.

In particular, Kato et al. cover B cell-associated diseases that manifest in the respiratory system, such as systemic lupus erythematosus [SLE], and the targeted therapies that are currently approved for treatment or undergoing clinical trials.  A few highlights:

•    Anti-IL-9, a Th cytokine that acts on B-cells and mast cells, is in clinical trials as a therapy for asthma.
•    Anti-IL-6 receptor, approved for use in the treatment of rheumatoid arthritis, has been proposed as therapy for asthma and COPD, and is in clinical trials for cancer treatment.
•    Anti-IFN╬▒ is in clinical trials for SLE.
•    Anti-BAFF has been approved for the treatment of SLE.

The authors review B lymphocyte organization in the airway, critical airway immunoglobulins and associated lung diseases, such as the hyper-Ig syndromes, and the commonality of excessive B cell expansion with subsequent loss of self-tolerance that characterizes certain lung diseases such as hypersensitivity pneumonitis, rheumatoid arthritis, and Sjogren’s disease.  They conclude posing important questions that remain, which are stalling the development of therapies. 



A clinical picture of recalcitrant chronic rhinosinusitis


Dr. Daniel Hamilos [p1263-1264] discusses  the importance of microbes (viruses, bacteria and fungi) in chronic rhinosinusitis [CRS] in this month’s issue [Journal of Allergy and Clinical Immunology 2013; 131(4):1263-1264] Starting with a case report, the author reviews the current state of knowledge of CRS with [CRSwNP] and without [CRSsNP] nasal polyposis and further discusses the definitions of refractory and recalcitrant CRS.  CME questions are included at the end of the article.

Dr. Hamilos notes that eosinophilic inflammation is present to some degree in both CRSwNP and CRSsNP patients, whereas neutrophilia is more common in CRSsNP.  While there is little evidence for persistent viral infection in CRS, there is evidence for persistent infection with Staphylococcus aureus and/or Pseudomonas aeruginosa in sinus tissue  in roughly 80% of refractory CRS cases.  The presence of these bacteria is often found in association with “biofilm” formation.  The author discusses biofilm and studies showing that its presence is associated with more severe disease and poorer outcomes.  The fungus Alternaria is also more frequently detected in CRS tissues than in tissues from healthy patients. 

The author discusses the various components of innate and adaptive immunity that function in response to microbial colonization or infection in CRS patients.  Examples of key observations include the presence of  a Th2 inflammatory bias in CRSwNP that negatively impacts TLR-9 function.  Dr. Hamilos wraps up commenting that more precise clinical characterization of CRS patients based on their  microbial and immunological phenotype is needed to assist clinicians in designing more effective treatment strategies.