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Biomedical subjects

M M Black

Publications and source records attributed to M M Black.

At least 19 recordsLinked to original sources
PubMed2006

Polymorphic eruption of pregnancy: clinicopathology and potential trigger factors in 181 patients.

BACKGROUND: Polymorphic eruption of pregnancy (PEP; synonym: pruritic urticarial papules and plaques of pregnancy) is the most common specific dermatosis of pregnancy. However, its clinical characterization is controversial and its pathogenesis uncertain. OBJECTIVES: To evaluate clinical characteristics of and potential trigger factors for PEP in a large mixed ethnic population. METHODS: A retrospective analysis of epidemiological, clinical, immunopathological and obstetric findings in 181 patients with PEP seen at two university-based dermatological hospitals in Graz, Austria, and London, U.K. RESULTS: PEP mainly affected white (88%) primigravidae (70%) in late pregnancy (83%; mean +/- SD onset 34 +/- 5 weeks) or the immediate postpartum period (15%). The most commonly involved sites were the abdomen and proximal thighs (97%). Involvement of the whole skin, including the face, palms and soles, was only rarely observed. While pruritic urticarial papules and plaques were the main morphological features at disease onset (98%), more than one-half of the patients (51%) later developed polymorphous features including erythema, vesicles, and targetoid and eczematous lesions. Topical treatment with corticosteroids and emollients was sufficient to control symptoms in the majority of patients, and skin lesions resolved after a mean +/- SD of 4 +/- 3 weeks. Multiple gestation pregnancies were observed in 13% of cases, excessive maternal weight gain in 78%. CONCLUSIONS: Our data confirm the benign, self-limiting nature of PEP and its favourable outcome for both the mother and the fetus. For the first time, we have documented a characteristic change in morphology with disease progression. The evidence of polymorphous clinical features in more than one-half of the patients favours the use of the term PEP. Multiple gestation pregnancies and excessive maternal weight gain, but not fetal weight and sex, were found to be significantly associated with PEP.

Adolescent↗
PubMed2006

Evidence of an association between desmoglein 3 haplotypes and pemphigus vulgaris.

BACKGROUND: Pemphigus vulgaris (PV, OMIM 169610) is a severe blistering disorder of the skin and mucous membranes, caused by the production of autoantibodies directed against the epithelial adhesive protein desmoglein 3. Although an association between PV and HLA class II alleles has been established, the genetic factors predisposing to the disease remain poorly understood, the rarity of PV hampering the recruitment of substantial patient cohorts. OBJECTIVES: To investigate DSG3 as a candidate PV susceptibility gene. METHODS: We examined five DSG3 single nucleotide polymorphisms (rs8085532, rs3911655, rs3848485, rs3794925 and rs1466379) in two case-control datasets respectively originating from the U.K. (62 PV patients, 154 controls) and northern India (28 patients, 98 controls). RESULTS: In the U.K. sample, we observed a significant association between PV and the DSG3*TCCTC haplotype (Fisher's exact test P = 0.002). A related haplotype (DSG3*TCCCC) was associated with PV in the Indian dataset (P = 0.002). We also found that all British and Indian patients bearing DSG3 risk haplotypes carried at least one copy of a PV-associated HLA allele. CONCLUSIONS: These results suggest that genetic variation of DSG3 may be an additive risk factor predisposing to PV and warrant further investigations of this gene.

Case-Control Studies↗
PubMed2006

Bullous pemphigoid antigen II (BP180) and its soluble extracellular domains are major autoantigens in mucous membrane pemphigoid: the pathogenic relevance to HLA class II alleles and disease severity.

BACKGROUND: Mucous membrane pemphigoid (MMP), a chronic autoimmune subepithelial blistering disease, is associated with circulating IgG and/or IgA autoantibodies against several basement membrane zone antigens. The heterogeneity of clinical presentation and diversity of target autoantigens have contributed to difficulties in characterizing this condition immunologically. OBJECTIVES: To analyse serum autoantibody profile and HLA class II alleles in MMP patients and to correlate this with the clinical presentation of disease. METHODS: Well-defined subgroups consisting of 124 patients with MMP were examined for IgG and IgA reactivity with immunoblotting using human epidermal, dermal and placental amnion proteins. The results were further analysed on the basis of detailed clinical (sites of involvement and disease severity) and immunopathological criteria (immunofluorescence study and HLA class II alleles). RESULTS: Immunoblot assay revealed that the majority of MMP patients had IgG (93 of 124, 75%) and/or IgA autoantibodies (63 of 124, 51%) to BP180 (including its soluble ectodomains, 120-kDa LAD-1 and 97-kDa LABD97 antigens). Other antigens targeted predominantly by IgG autoantibodies included: BP230 in 34 (27%), beta4 integrin in 26 (21%), and laminin 5 in three (2%). All the BP230+ sera and 23 (88%) beta4 integrin+ sera also reacted with at least one of the BP180 antigens. Over 85% of patients with reactivity to beta4 integrin had ocular involvement. In most cases of MMP, more severe clinical features were associated with antibody reactivity to multiple basement membrane zone antigens, as well as reactivity to multiple BP180 component antigens. Dual BP180/LAD-1 reactivity with IgG and IgA was associated with a more severe phenotype. In addition, the subset-dependent autoantibody reactivity correlated well with specific HLA class II alleles, DQB1*0301, DRB1*04 and DRB1*11. CONCLUSIONS: Our results confirmed that BP180 is a major autoantigen targeted by the sera of patients with MMP. The disease-prevalent HLA class II alleles and humoral autoimmune response against the particular subsets of antigenic epitope(s) within BP180 ectodomain may contribute to the clinicopathological significance and disease severity of MMP.

Adult↗
PubMed2005

Discoid lupus erythematosus with secondary amyloidosis.

BACKGROUND: Secondary localized cutaneous amyloidosis is a clinically unapparent phenomenon associated with various cutaneous pathologies, usually tumours of epidermal origin. The amyloid is thought to be derived from keratinocytes. OBJECTIVES: To characterize the amyloid deposition observed incidentally within lesional biopsies from three patients with discoid lupus erythematosus (DLE), and retrospectively to study the phenomenon within DLE skin samples. METHODS: Localized amyloid deposition was observed in three cases of DLE by immunofluorescence studies, and these cases were further studied by histology and immunohistochemistry using a monoclonal anticytokeratin antibody. Retrospective histological review of DLE tissue specimens archived over 12 months was performed to look for evidence of previously undetected amyloid. RESULTS: Amyloid deposition was confirmed histologically in the three index cases by staining with Congo red and thioflavin T. Positive staining with an anticytokeratin antibody demonstrated the epidermal origin of the amyloid protein. Of the 18 archived cases reviewed amyloid was retrospectively detected in one sample. CONCLUSIONS: Secondary cutaneous amyloidosis of keratinocyte origin can be seen in DLE lesions. It may be a not infrequent occurrence and may remain under-reported. We discuss the possible role of disease chronicity and colloid body degradation in the pathogenesis of amyloidosis.

Amyloid↗
PubMed2005

Collagen XVII/BP180: a collagenous transmembrane protein and component of the dermoepidermal anchoring complex.

Collagen XVII, or BP180, is a collagenous transmembrane protein and a structural component of the dermoepidermal anchoring complex. Molecular studies reveal that it has a globular cytosolic amino-terminal domain and flexible-rod extracellular carboxyterminal domain. The extracellular portion of collagen XVII is constitutively shed from the cell surface by ADAMs (proteinases that contain adhesive and metalloprotease domains). Cell biological analyses suggest that collagen XVII functions as a cell-matrix adhesion molecule through stabilization of the hemidesmosome complex. This concept is supported by investigations into human diseases of the dermoepidermal junction, in which collagen XVII is either genetically defective or absent (as in some forms of nonlethal junctional epidermolysis bullosa). Autoantibodies against collagen XVII (BP180) are seen in bullous pemphigoid, pemphigoid gestationis, mucous membrane pemphigoid, linear IgA disease, lichen planus pemphigoides and pemphigoid nodularis. In vivo and in vitro studies provide evidence for a pathogenic role of these autoantibodies, and suggest that the serum level and epitope specificity of these antibodies influences disease severity and phenotype. This review summarizes the structural and biological features of collagen XVII and its role in diseases of the basement membrane zone.

Autoantigens↗
PubMed2004

Evaluation of a BP180-NC16a enzyme-linked immunosorbent assay in the initial diagnosis of bullous pemphigoid.

BACKGROUND: Bullous pemphigoid (BP) is the most common subepidermal immunobullous disease, characterized by circulating IgG autoantibodies targeting BP180 and BP230 hemidesmosomal proteins. Several immunological studies have demonstrated that the membrane proximal noncollagenous domain NC16a of BP180 is the immunodominant region targeted by BP autoantibodies. Recently, a commercial BP180 NC16a-specific enzyme-linked immunosorbent assay (ELISA) has become available for detecting pathogenic anti-BP180 autoantibodies in BP sera. However, it remains unclear whether the diagnostic potential of the ELISA is equivalent to that of the 'gold-standard' diagnostic technique of immunofluorescence (IF). OBJECTIVES: To examine the usefulness of a commercially available BP180-NC16a ELISA in the initial serodiagnosis of BP. METHODS: Sera from a large cohort of patients with BP (n = 102) and control subjects (age- and sex-matched normal volunteers, n = 60; pemphigus foliaceus, n = 18; pemphigus vulgaris, n = 16) were assayed by BP180-NC16a ELISA. All BP sera were obtained at presentation before initiation of systemic immunosuppressive therapy. The values of IgG antibody levels measured by ELISA were compared with those measured by indirect IF on salt-split skin. Results Receiver operating characteristic analysis was used to calculate the cut-off value for the ELISA in the diagnosis of BP which maximizes both sensitivity and specificity, and to estimate the diagnostic accuracy of the ELISA as represented by the area under the curve (AUC = 0.965). A cut-off value of 9 was associated with a sensitivity of 89% (91 of 102 BP sera showed a positive result) and a specificity of 98%. Fifty-eight of 60 normal controls and all the pemphigus sera showed a negative result. There was a correlation between the mean ELISA values and indirect IF titres (Spearman rank correlation 0.286; P = 0.004). CONCLUSIONS: Our results suggest that the BP180-NC16a ELISA is a useful tool for the detection of pathogenic anti-BP180 IgG autoantibodies at the initial disease stage of BP. Because it is not only highly sensitive and specific, but is also easy to perform, is objective, and semiquantitative, the ELISA may provide valuable information for the accurate and reliable serodiagnosis of BP.

Aged↗
PubMed2004

Bullous subacute cutaneous lupus erythematosus.

We describe a 59-year-old woman, with a history of autoimmune disease and disseminated uterine leiomyosarcoma, who developed a photoaggravated, blistering skin eruption. An initial rash, at the outset of treatment with chemo- and radiotherapy, resembled erythema multiforme. Review of the original skin biopsy showed it to be subacute cutaneous lupus erythematosus. There were no systemic symptoms or signs to suggest systemic lupus erythematosus. The much later photoaggravated rash consisted mainly of bullae and eventual epidermal denuding which resembled toxic epidermal necrolysis. We propose that the clinical and histological diagnosis is one of bullous subacute cutaneous lupus erythematosus in a patient with no other features of systemic lupus erythematosus.

Antineoplastic Agents↗
PubMed2004

Characterization of IgG autoantibodies to extracellular matrix protein 1 in lichen sclerosus.

Although the precise aetiology of lichen sclerosus is unknown, evidence for an autoimmune basis to the disorder is emerging. Indeed, circulating IgG autoantibodies to the glycoprotein extracellular matrix protein 1 (ECM1) have been demonstrated in the sera of about 75% of affected individuals. To assess this humoral immune response further, immunoblotting was performed using bacterial recombinant proteins spanning different domains of the ECM1 protein. The aim was to identify autoantibody-reactive sites recognized by 90 lichen sclerosus sera. The subclass distribution of anti-ECM1 IgG autoantibodies was also determined in 54 lichen sclerosus sera. Immunoblotting showed that the IgG autoantibodies from lichen sclerosus patients recognize multiple antigenic reactive sites on the ECM1 protein within both the amino terminus (50/90, 55.6%) and the protein loop cysteine-rich repeat domains (54/90, 60%), although few sera (7/90, 7.8%) had antibodies to the carboxyl terminus of ECM1. IgG subclass analysis revealed that the anti-ECM1 autoantibodies belong predominantly to the IgG(2) subclass (48/54, 88.9%), either IgG(2) alone (28/54, 51.9%) or in combination with one or more other IgG subclasses. No correlation was found between the site(s) of the ECM1 epitopes or the anti-ECM1 IgG profile and any specific clinical parameters. Nevertheless, characterization of anti-ECM1 antibodies does provide further insight into humoral immune responses and understanding disease mechanisms in lichen sclerosus.

Adult↗