BAFF (BLyS, TALL-1, THANK, zTNF4) is a member of the TNF superfamily that specifically regulates B lymphocyte proliferation and survival. Mice transgenic (Tg) for BAFF develop an autoimmune condition similar to systemic lupus erythematosus. We now demonstrate that BAFF Tg mice, as they age, develop a secondary pathology reminiscent of Sjogren's syndrome (SS), which is manifested by severe sialadenitis, decreased saliva production, and destruction of submaxillary glands. In humans, SS also correlates with elevated levels of circulating BAFF, as well as a dramatic upregulation of BAFF expression in inflamed salivary glands. A likely explanation for disease in BAFF Tg mice is excessive survival signals to autoreactive B cells, possibly as they pass through a critical tolerance checkpoint while maturing in the spleen. The marginal zone (MZ) B cell compartment, one of the enlarged B cell subsets in the spleen of BAFF Tg mice, is a potential reservoir of autoreactive B cells. Interestingly, B cells with an MZ-like phenotype infiltrate the salivary glands of BAFF Tg mice, suggesting that cells of this compartment potentially participate in tissue damage in SS and possibly other autoimmune diseases. We conclude that altered B cell differentiation and tolerance induced by excess BAFF may be central to SS pathogenesis.

/pdf/association-of-baff-blys-overexpression-and-altered-b-cell-4db4dm5ot8.pdf

Association of BAFF/BLyS overexpression and altered B cell differentiation with Sjögren’s syndrome

Atopic dermatitis (AD) is a chronic, pruritic, inflammatory dermatosis that affects up to 25% of children and 2% to 3% of adults. This guideline addresses important clinical questions that arise in the management and care of AD, providing updated and expanded recommendations based on the available evidence. In this first of 4 sections, methods for the diagnosis and monitoring of disease, outcomes measures for assessment, and common clinical associations that affect patients with AD are discussed. Known risk factors for the development of disease are also reviewed.

http://blackbook.com.br/wp-content/uploads/2014/02/OK-aad-2012-atopic-dermatitis-guideline-part-1-article-in-press.pdf

Guidelines of care for the management of atopic dermatitis: section 1. Diagnosis and assessment of atopic dermatitis.

The innate immune system is crucial for initiation and amplification of inflammatory responses. During this process, phagocytes are activated by PAMPs that are recognized by PRRs. Phagocytes are also activated by endogenous danger signals called alarmins or DAMPs via partly specific, partly common PRRs. Two members of the S100 protein family, S100A8 and S100A9, have been identified recently as important endogenous DAMPs. The complex of S100A8 and S100A9 (also called calprotectin) is actively secreted during the stress response of phagocytes. The association of inflammation and S100A8/S100A9 was discovered more than 20 years ago, but only now are the molecular mechanisms involved in danger signaling by extracellular S100A8/S100A9 beginning to emerge. Taking advantage of mice lacking the functional S100A8/S100A9 complex, these molecules have been identified as endogenous activators of TLR4 and have been shown to promote lethal, endotoxin-induced shock. Importantly, S100A8/S100A9 is not only involved in promoting the inflammatory response in infections but was also identified as a potent amplifier of inflammation in autoimmunity as well as in cancer development and tumor spread. This proinflammatory action of S100A8/S100A9 involves autocrine and paracrine mechanisms in phagocytes, endothelium, and other cells. As a net result, extravasation of leukocytes into inflamed tissues and their subsequent activation are increased. Thus, S100A8/S100A9 plays a pivotal role during amplification of inflammation and represents a promising new therapeutic target.

https://jlb.onlinelibrary.wiley.com/doi/pdf/10.1189/jlb.1008647

The endogenous Toll-like receptor 4 agonist S100A8/S100A9 (calprotectin) as innate amplifier of infection, autoimmunity, and cancer

Functional roles of S100 proteins, calcium-binding proteins of the EF-hand type

This guideline was developed as a joint interdisciplinary European project, including physicians from all relevant disciplines as well as patients. It is a consensus-based guideline, taking available evidence from other guidelines, systematic reviews and published studies into account. This second part of the guideline covers antimicrobial therapy, systemic treatment, allergen-specific immunotherapy, complementary medicine, psychosomatic counselling and educational interventions, whereas the first part covers methods, patient perspective, general measures and avoidance strategies, basic emollient treatment and bathing, dietary intervention, topical anti-inflammatory therapy, phototherapy and antipruritic therapy. Management of AE must consider the individual clinical variability of the disease. Systemic immunosuppressive treatment with cyclosporine, methotrexate, azathioprine and mycophenolic acid is established option for severe refractory cases, and widely available. Biologicals targeting the T helper 2 pathway such as dupilumab may be a safe and effective, disease-modifying alternative when available. Oral drugs such as JAK inhibitors and histamine 4 receptor antagonists are in development. Microbial colonization and superinfection may cause disease exacerbation and can require additional antimicrobial treatment. Allergen-specific immunotherapy with aeroallergens may be considered in selected cases. Psychosomatic counselling is recommended especially in stress-induced exacerbations. Therapeutic patient education ('Eczema school') is recommended for children and adult patients. General measures, basic emollient treatment, bathing, dietary intervention, topical anti-inflammatory therapy, phototherapy and antipruritic therapy have been addressed in the first part of the guideline.

https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdv.14891

Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part I.

https://www.jaad.org/article/S0190-9622(86)70152-7/pdf

Clinical and laboratory studies

The purpose of this study was to investigate whether fish oil and/or corn oil had a beneficial effect on the clinical state of atopic dermatitis, and to evaluate the dietary intake of nutrients in this group of patients. In a double-blind, multicentre study lasting 4 months, during wintertime, 145 patients with moderate to severe atopic dermatitis were randomly assigned to receive either 6 g/day of concentrated n-3 fatty acids, or an isoenergetic amount of corn oil. As local treatment, only an emollient cream or hydrocortisone cream was allowed. The fatty acid pattern in serum phospholipids, and the dietary intake of nutrients were monitored in a subgroup of patients, and the results were compared with a group of patients with psoriasis. The overall clinical score, as evaluated by the physicians, improved during the trial by 30% in the fish oil (P < 0.001) and 24% in the corn oil group (P < 0.001). This was also consistent with the results from a selected skin area, and it was further confirmed by the total subjective clinical score reported by the patients. There were no significant differences in the clinical scores between the two groups at baseline, and at the end of the study. In the fish oil group, the amount of n-3 fatty acids in serum phospholipids was significantly increased at the end of the trial, compared with pretreatment values (P < 0.001), whereas the level of n-6 fatty acids was decreased (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Dietary supplementation with very long‐chain n‐3 fatty acids in patients with atopic dermatitis. A double‐blind, multicentre study

The L1 antigen is a major cytosol component of human granulocytes that may also be expressed by macrophages and epithelial cells. Its epidermal and dermal occurrence was investigated in formalin-fixed routine biopsy material from eleven different inflammatory skin disorders. Localization was performed with a rabbit antiserum to L1 applied in an unlabeled antibody peroxidase-antiperoxidase method. L1 antigen was not found in normal skin except in epithelial cells of pilosebaceous units. However, epidermal L1 antigen was demonstrated in every biopsy specimen from lupus erythematosus, lichen planus, dermatitis herpetiformis, and atopic dermatitis, whereas granuloma annulare test results were usually negative. The occurrence of dermal L1 antigen depended on the composition of the inflammatory infiltrate; specimens rich in neutrophilic granulocytes (e.g., dermatitis herpetiformis) were particularly strongly stained. Extracellular dermal staining was also seen, especially in areas adjacent to accumulations of positive leukocytes. The varying epidermal occurrence of Ll antigen in skin diseases probably signified different degrees of proliferative activity of the epithelial cells and could apparently not be ascribed to uptake from the dermis.

Per Thune

Papers

Clinical and laboratory studies

Dietary supplementation with very long‐chain n‐3 fatty acids in patients with atopic dermatitis. A double‐blind, multicentre study

Epidermal and dermal distribution of a myelomonocytic antigen (L1) shared by epithelial cells in various inflammatory skin diseases

Allergic contact dermatitis in an aroma therapist with multiple sensitizations to essential oils

Contact allergy due to tea tree oil and cross-sensitization to colophony.