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

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

Climate geoengineering: issues of path-dependence and socio-technical lock-in

As academic and policy interest in climate geoengineering grows, the potential irreversibility of technological developments in this domain has been raised as a pressing concern. The literature on socio-technical lock-in and path dependence is illuminating in helping to situate current concerns about climate geoengineering and irreversibility in the context of academic understandings of historical socio-technical development and persistence. This literature provides a wealth of material illustrating the pervasiveness of positive feedbacks of various types (from the discursive to the material) leading to complex socio-technical entanglements which may resist change and become inflexible even in the light of evidence of negative impacts. With regard to climate geoengineering, there are concerns that geoengineering technologies might contribute so-called ‘carbon lock-in’, or become irreversibly ‘locked-in’ themselves. In particular, the scale of infrastructures that geoengineering interventions would require, and the issue of the so-called ‘termination effect’ have been discussed in these terms. Despite the emergent and somewhat ill-defined nature of the field, some authors also suggest that the extant framings of geoengineering in academic and policy literatures may already demonstrate features recognizable as forms of cognitive lock-in, likely to have profound implications for future developments in this area. While the concepts of path-dependence and lock-in are the subject of ongoing academic critique, by drawing analytical attention to these pervasive processes of positive feedback and entanglement, this literature is highly relevant to current debates around geoengineering

World Workshop on Oral Medicine VIII: Development of a core outcome set for oral lichen planus: a systematic review of outcome domains

Objective: There is a lack of consensus regarding clinician- and patient-reported oral lichen planus (OLP) outcomes. The World Workshop on Oral Medicine Outcomes Initiative for the Direction of Research (WONDER) Project aims to develop a core outcome set (COS) for OLP, which would inform the design of clinical trials and, importantly, facilitate meta-analysis, leading to the establishment of more robust evidence for the management of this condition and hence improved patient care. Study Design: Ovid MEDLINE, Embase, CINAHL, CENTRAL, and Clinicaltrials.gov were searched for interventional studies (randomized controlled trials, controlled clinical trials, and case series including ≥5 participants) on OLP and oral lichenoid reactions published between January 2001 and March 2022 without language restriction. All reported primary and secondary outcomes were extracted. Results: The searches yielded 9,135 records, and 291 studies were included after applying the inclusion criteria. A total of 422 outcomes were identified. These were then grouped based on semantic similarity, condensing the list to 69 outcomes. The most frequently measured outcomes were pain (51.9%), clinical grading of the lesions (29.6%), lesion size/extension/area (27.5%), and adverse events (17.5%). Conclusion: As a first step in developing a COS for OLP, we summarized the outcomes that have been used in interventional studies over the past 2 decades, which are numerous and heterogeneous.S

World Workshop on Oral Medicine VIII: Development of a core outcome set for oral lichen planus: the patient perspective

Objective: This study aimed to explore the lived experience of patients with oral lichen planus (OLP) and investigate what treatment-related outcomes are the most important to them and should be included in a core outcome set (COS) for OLP. Study Design: A qualitative study involving focus group work with 10 participants was conducted. Interviews with each focus group were held twice: session 1 explored the lived experience of patients with OLP, and session 2 allowed patients to review a summary of the outcome domains used in the OLP literature to date. The discussions were recorded, transcribed verbatim, and analyzed using framework analysis. Results: In session 1, 4 themes and 8 sub-themes emerged from the data analysis. An additional outcome, ‘knowledge of family and friends,’ was suggested in session 2. Conclusions: We have gained valuable insight into the lived experience of patients with OLP via this qualitative study. To our knowledge, this study is the first to explore the patient perspective on what should be measured in clinical trials on OLP, highlighting an important additional suggested outcome. This additional outcome will be voted upon in a consensus process to determine a minimum COS for OLPS

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