Autoantibody detection for diagnosis in direct immunofluorescence negative mucous membrane pemphigoid: ocular and other sites compared

Objective: To assess whether a panel of serum pemphigoid autoantibody tests could be used to confirm an immunopathological diagnosis of mucous membrane pemphigoid (MMP) in direct immunofluorescent negative (DIF-) MMP patients. / Design: Prospective cross-sectional study. / Subjects and controls: 76 patients with MMP involving ocular and non-ocular sites with 45 matched controls. / Tests: Enzyme linked immunosorbent assays (ELISA) for BP180 and BP230 (MBL International®), IgA and IgG indirect immunofluorescence on human salt-split skin (IIF SSS) and the keratinocyte footprint assay for anti-laminin 332 antibodies. / Main outcome measures: Sensitivity and specificity of autoantibody detection; significant differences for individual tests and test combinations for MMP involving different sites. / Results: All DIF- Cases (24/76, 31.8%) had either ocular only disease or ocular involvement in multi-site disease. Serum pemphigoid autoantibodies were detected in 29/76 (38.2%) of all MMP patients compared to 3/45 (6.7%) of controls. Autoantibody reactivity detected by any one or more of the tests was present in 6/24 (25%) DIF- cases compared to 22/49 (44.9%) in DIF positive (DIF+). Compared to controls ocular only MMP serum reactivity was not significantly different for any test or test combination whereas DIF- multisite ocular MMP differed for one ELISA and 3/7 test combinations. By contrast, for DIF+ non ocular MMP all the individual tests, apart from IgA IIF, and all test combinations were significantly different compared to controls. For the whole MMP cohort the sensitivity of all tests was low having a maximum of 21.05% for BP180 reactivity, increasing to 38.16% for an optimal test combination. Disease activity was strongly associated with positive serology findings. / Conclusions: Pemphigoid serum autoantibody tests did not provide alternative immunopathological evidence of MMP in ocular only MMP patients but had limited value in DIF- multisite ocular MMP. The requirement for immunopathological confirmation of MMP by autoantibody detection is inappropriate for DIF- ocular only MMP resulting in missed diagnoses, delayed therapy and poor outcomes. Alternative diagnostic criteria for MMP with ocular involvement are required, to exclude the other causes of scarring conjunctivitis, until more sensitive and specific immunopathology tests become available

When to Use Transdisciplinary Approaches for Environmental Research

Transdisciplinary research (TDR) can help generate solutions to environmental challenges and enhance the uptake of research outputs, thus contributing to advance sustainability in social-ecological systems. Our aim is to support investment decisions in TDR; more specifically, to help funders, researchers, and research users to decide when and why it is most likely to be worth investing in TDR approaches. To achieve our aim, we: 1) define TDR and use a decision tree comparing it with alternative modes of research (i.e., basic, applied, disciplinary, multi-disciplinary, and interdisciplinary research) to help researchers and funders distinguish TDR from other research modes; 2) identify features of the research problem and context (complexity, diverse knowledge systems, contestation, power imbalance, and disagreement on the need for transformative change) where a TDR approach could be more appropriate than the alternative research modes; and 3) explore the idea that the intensity of the contextual features in (2), together with the problem at hand, will help determine where a research project stands in a continuum from low- to high-TDR. We present five studies exemplifying lower- to higher-TDR approaches that are distinguished by: 1) the number and variety of research participants engaged; 2) the strength of involvement of non-academic actors; and 3) the number and variety of disciplines and knowledge systems involved in the research

Invasive Andropogon gayanus (gamba grass) is an ecosystem transformer of nitrogen relations in Australian savanna

The African grass Andropogon gayanus Kunth. is invading Australian savannas, altering their ecological and biogeochemical function. To assess impacts on nitrogen (N) cycling, we quantified litter decomposition and N dynamics of grass litter in native grass and A. gayanus invaded savanna using destructive in situ grass litter harvests and litterbag incubations (soil surface and aerial position). Only 30% of the A. gayanus in situ litter decomposed, compared to 61% of the native grass litter, due to the former being largely comprised of highly resistant A. gayanus stem. In contrast to the stem, A. gayanus leaf decomposition was approximately 3- and 2-times higher than the dominant native grass, Alloteropsis semilata at the surface and aerial position, respectively. Lower initial lignin concentrations, and higher consumption by termites, accounted for the greater surface decomposition rate of A. gayanus. N flux estimates suggest the N release of A. gayanus litter is insufficient to compensate for increased N uptake and N loss via fire in invaded plots. Annually burnt invaded savanna may lose up to 8.2% of the upper soil N pool over a decade. Without additional inputs via biological N fixation, A. gayanus invasion is likely to diminish the N capital of Australia's frequently burnt savannas

European guidelines (S3) on diagnosis and management of mucous membrane pemphigoid, initiated by the European Academy of Dermatology and Venereology – Part I

This guideline on mucous membrane pemphigoid (MMP) has been elaborated by the Task Force for Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology (EADV) with a contribution of physicians from all relevant disciplines and patient organizations. It is a S3 consensus-based guideline encompassing a systematic review of the literature until June 2019 in the MEDLINE and EMBASE databases. This first part covers methodology, the clinical definition of MMP, epidemiology, MMP subtypes, immunopathological characteristics, disease assessment and outcome scores. MMP describes a group of autoimmune skin and mucous membrane blistering diseases, characterized by a chronic course and by predominant involvement of the mucous membranes, such as the oral, ocular, nasal, nasopharyngeal, anogenital, laryngeal and oesophageal mucosa. MMP patients may present with mono- or multisite involvement. Patients’ autoantibodies have been shown to be predominantly directed against BP180 (also called BPAG2, type XVII collagen), BP230, laminin 332 and type VII collagen, components of junctional adhesion complexes promoting epithelial stromal attachment in stratified epithelia. Various disease assessment scores are available, including the Mucous Membrane Pemphigoid Disease Area Index (MMPDAI), the Autoimmune Bullous Skin disorder Intensity Score (ABSIS), the ‘Cicatrising Conjunctivitis Assessment Tool’ and the Oral Disease Severity Score (ODSS). Patient-reported outcome measurements (PROMs), including DLQI, ABQOL and TABQOL, can be used for assessment of quality of life to evaluate the effectiveness of therapeutic interventions and monitor disease course

European guidelines (S3) on diagnosis and management of mucous membrane pemphigoid, initiated by the European Academy of Dermatology and Venereology – Part I

This guideline on mucous membrane pemphigoid (MMP) has been elaborated by the Task Force for Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology (EADV) with a contribution of physicians from all relevant disciplines and patient organizations. It is a S3 consensus-based guideline encompassing a systematic review of the literature until June 2019 in the MEDLINE and EMBASE databases. This first part covers methodology, the clinical definition of MMP, epidemiology, MMP subtypes, immunopathological characteristics, disease assessment and outcome scores. MMP describes a group of autoimmune skin and mucous membrane blistering diseases, characterized by a chronic course and by predominant involvement of the mucous membranes, such as the oral, ocular, nasal, nasopharyngeal, anogenital, laryngeal and oesophageal mucosa. MMP patients may present with mono- or multisite involvement. Patients’ autoantibodies have been shown to be predominantly directed against BP180 (also called BPAG2, type XVII collagen), BP230, laminin 332 and type VII collagen, components of junctional adhesion complexes promoting epithelial stromal attachment in stratified epithelia. Various disease assessment scores are available, including the Mucous Membrane Pemphigoid Disease Area Index (MMPDAI), the Autoimmune Bullous Skin disorder Intensity Score (ABSIS), the ‘Cicatrising Conjunctivitis Assessment Tool’ and the Oral Disease Severity Score (ODSS). Patient-reported outcome measurements (PROMs), including DLQI, ABQOL and TABQOL, can be used for assessment of quality of life to evaluate the effectiveness of therapeutic interventions and monitor disease course

European Guidelines (S3) on diagnosis and management of mucous membrane pemphigoid, initiated by the European Academy of Dermatology and Venereology – Part II

This guideline has been initiated by the task force Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology, including physicians from all relevant disciplines and patient organizations. It is a S3 consensus-based guideline that systematically reviewed the literature on mucous membrane pemphigoid (MMP) in the MEDLINE and EMBASE databases until June 2019, with no limitations on language. While the first part of this guideline addressed methodology, as well as epidemiology, terminology, aetiology, clinical presentation and outcome measures in MMP, the second part presents the diagnostics and management of MMP. MMP should be suspected in cases with predominant mucosal lesions. Direct immunofluorescence microscopy to detect tissue-bound IgG, IgA and/or complement C3, combined with serological testing for circulating autoantibodies are recommended. In most patients, serum autoantibodies are present only in low levels and in variable proportions, depending on the clinical sites involved. Circulating autoantibodies are determined by indirect IF assays using tissue substrates, or ELISA using different recombinant forms of the target antigens or immunoblotting using different substrates. The major target antigen in MMP is type XVII collagen (BP180), although in 10–25% of patients laminin 332 is recognized. In 25–30% of MMP patients with anti-laminin 332 reactivity, malignancies have been associated. As first-line treatment of mild/moderate MMP, dapsone, methotrexate or tetracyclines and/or topical corticosteroids are recommended. For severe MMP, dapsone and oral or intravenous cyclophosphamide and/or oral corticosteroids are recommended as first-line regimens. Additional recommendations are given, tailored to treatment of single-site MMP such as oral, ocular, laryngeal, oesophageal and genital MMP, as well as the diagnosis of ocular MMP. Treatment recommendations are limited by the complete lack of high-quality randomized controlled trials

The challenge of rural life nostalgia: barriers in redevelopment of Malay Reserve Land (MRL) in Klang Valley

The development of Malay reserve land is a nationwide issue which can be overcome through better understanding of the existing barriers. While many barriers have been examined, the challenges relating to land owner expectations and preferences has not been thoroughly examined. Using Kg Sungai Penchala in the capital city Kuala Lumpur as a case, this research used a structured interview survey of 258 respondents representing both owners and tenants. Statistical analysis demonstrates that majority of the land owners (individuals) rejected the idea to further develop the land. The land owners preferred to maintain the village status quo and they were satisfied with the current development level in the village. Only a minority of respondents agreed that the land should be developed and instead perceived that re-development of this Malay Reserve Land of Kg Sungai Penchala would be able to raise their quality of life. The restriction is much preferred by the land owners who preferred the current style of village living. Thus, immediate re-development of the area is not warranted and the preference of the land owners represents a strong barrier