Allergic reactions.
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Anesthesia, Dental↗
Biomedical subjects
S J Challacombe
Publications and source records attributed to S J Challacombe.
Characteristics of human IgA and IgM genes used by plasma cells in the salivary gland resemble those used in duodenum but not those used in the spleen.
Immunologically, the parotid salivary gland is an effector site that secretes large quantities of polyspecific Abs into the saliva, mainly of the IgA isotype. It is considered to be part of the common mucosal immune system but the inductive site for the Ab-producing cells of the salivary gland has not yet been clearly identified. The origin and diversity of cells of B lineage can be investigated by analyzing their Ig heavy chain genes (IgH). We have obtained sequences of IgM and IgA VH4-34 genes from plasma cells in human salivary gland, duodenal lamina propria, and splenic red pulp. Related sequences were found in different areas sampled within each tissue studied, indicating that the plasma cells carrying these genes are widespread with limited diversity. Examples of related IgH genes that are isotype switched were also seen in the salivary gland. The genes from plasma cells of the salivary gland were highly mutated, as were duodenal plasma cell sequences. The level of mutation was significantly higher than that seen in splenic plasma cell sequences. Analysis of CDR3 regions showed that the sequences from salivary gland had significantly smaller CDR3 regions than sequences from spleen, due to differences in number and type of DH regions used. Sequences from duodenum also had smaller CDR3 regions. Therefore, plasma cells from human duodenum and salivary gland showed characteristics that differed from those of human splenic plasma cells.
Base Sequence↗
Multiple maxillary and mandibular exostoses associated with multiple dermatofibromas: a case report.
Exostoses of the maxilla and mandible are nodular protuberances of mature bone that need to be accurately distinguished from other more diagnostically significant lesions, notably exosteal osteomas. Multiple dermatofibromas are rare and may be associated with altered immune function. We report the case of an otherwise healthy 47-year-old woman who was first seen with multiple maxillary and mandibular exostoses associated with multiple dermatofibromas. This association has not been previously reported.
Exostoses↗
Serum and salivary antibodies to a mycobacterial 65-kDa stress protein are elevated in HIV-positive patients and modified by oral candidiasis.
Serum immunoglobulin G (IgG) and IgA, and salivary IgA antibodies to a mycobacterial stress protein (mSP65) were determined in human immunodeficiency virus (HIV)-positive patients, acquired immunodeficiency syndrome (AIDS) patients and HIV-negative controls with or without oral candidiasis. Serum IgG antibodies were elevated in patients with HIV infection and AIDS and especially in subjects with candidiasis compared with controls (P < 0.02, P < 0.005). This was not apparent with serum IgA. In the absence of candidiasis, salivary IgA antibodies were elevated in HIV-positive patients compared with AIDS (P < 0.005) patients and healthy controls (P = 0.001). The relative avidity of serum IgG antibodies to mSP65 in controls with candidiasis was lower than healthy controls (P < 0.0001). In saliva there was a decrease in the relative avidity of IgA antibodies in AIDS patients with candidiasis compared with HIV patients (P < 0.03). In patients without candidiasis, the relative avidity was higher in HIV patients than healthy controls (P = 0.02). The results suggest that HIV infection leads to raised serum and salivary antibodies to heat shock proteins. Concurrent Candida infection may modify both the titer and relative avidity differently for serum and saliva.
AIDS-Related Opportunistic Infections↗
The use of two substrates to improve the sensitivity of indirect immunofluorescence in the diagnosis of pemphigus.
The aim of this study was to re-evaluate indirect immunofluorescence (IIF) comparing two substrates, normal human skin (HS) and monkey oesophagus (MO) using serum from 29 pemphigus patients classified according to the presence of serum autoantibodies to either desmoglein (Dsg) 1 or Dsg3 detected by enzyme-linked immunosorbent assay (ELISA). Overall, the sensitivity of IIF was 83% on HS and 90% on MO. When data from both substrates were combined, the sensitivity increased to 100%. When sera from pemphigus foliaceus (PF) patients were studied, which contained Dsg1 antibodies only, the sensitivity of IIF was greatest on HS and titres were on average 4.8 doubling dilutions higher than on MO. In contrast, when sera containing autoantibodies only to Dsg3 from pemphigus vulgaris (PV) patients was studied, the sensitivity was greatest on MO and titres were on average 4.4 doubling dilutions higher than on HS. There was a significant correlation between Dsg1 antibody levels and IIF titres on HS and between Dsg3 antibody levels and IIF titres on MO. The investigation of immunobullous disorders in the future is likely to move towards antigen-specific techniques such as the Dsg ELISAs used in this study. However, in laboratories which currently rely on IIF for detecting pemphigus autoantibodies, the data presented in this study strongly suggest that two substrates should be used for IIF screening: one rich in Dsg1, such as HS, and the other rich in Dsg3, such as MO. This combination of substrates should not only increase the sensitivity of detecting pemphigus antibodies, but will aid in the differentiation of PV from PF. It is also possible that the data might be more useful for disease monitoring.
Animals↗
A study of desmoglein 1 autoantibodies in pemphigus vulgaris: racial differences in frequency and the association with a more severe phenotype.
BACKGROUND: Pemphigus vulgaris (PV) is characterized by pathogenic autoantibodies to desmoglein (Dsg) 3, but additional antibodies to Dsg1, the pemphigus foliaceus antigen, are detectable in some cases. OBJECTIVES: To investigate the clinical significance of the presence of both Dsg 1 and 3 antibodies. METHODS: In 79 subjects with PV, enzyme-linked immunosorbent assays were used to detect IgG autoantibodies reactive with the ectodomain of Dsg1 and Dsg3. RESULTS: There was a clear association between the clinical phenotype and the Dsg antibody profile. All subjects had Dsg3 autoantibodies and 61% had coexisting Dsg1 antibodies (Dsg3+/Dsg1+). PV limited entirely to the mucosal surfaces was seen only in Dsg3+/Dsg1- patients, while additional Dsg1 antibodies (Dsg3+/Dsg1+) predicted cutaneous in addition to mucosal involvement. Although minor cutaneous involvement was observed in most Dsg3+/Dsg1- patients, severe cutaneous involvement was seen only in Dsg3+/Dsg1+ patients. Dsg1 antibodies were detectable early in the course of disease and their appearance did not relate to the use of systemic therapy. The proportion of Dsg1+ patients was higher in those of Indian origin compared with white northern Europeans (P < 0.05). CONCLUSIONS: These data suggest that the presence of Dsg1 antibodies is predictive of a potentially more severe disease and that genetic factors may determine the Dsg antibody profile.
Autoantibodies↗
The management of oral lichen planus.
Oral lichen planus is a relatively common inflammatory disease affecting between 0.5% and 2.2% of the population in epidemiological studies. In contrast with cutaneous lichen planus (LP), in which the clinical course is often mild and resolves within 2 years, mucosal LP tends to follow a more chronic course often punctuated by acute exacerbations. Furthermore, although distinct clinical subtypes such as reticular, atrophic, hypertrophic and erosive forms are well recognized, more than one clinical phenotype may be seen at a time. The rare association with oral neoplasia should always be considered and high-risk patients must be kept under close observation. Thus the management of this disorder will vary widely both between patients, and for individual patients, with fluctuations in disease activity. Here we discuss the therapeutic options available and review the evidence for their use.
Adult↗
Diagnosis of pemphigus by ELISA: a critical evaluation of two ELISAs for the detection of antibodies to the major pemphigus antigens, desmoglein 1 and 3.
Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are characterized by autoantibodies to the desmosomal glycoproteins desmoglein 3 (Dsg 3) and Dsg 1 (Dsg 1), respectively. In this study, two enzyme-linked immunosorbent assays (ELISA) which detect IgG autoantibodies to Dsg 1 and Dsg 3 have been evaluated. A total of 317 normal and disease controls, 82 patients with PV and 25 with PF were studied. The Dsg 3 ELISA was positive in all 34 patients with untreated PV and the Dsg 1 ELISA was positive in all 10 with untreated PF. When patients undergoing treatment were included, the sensitivities fell to 95% and 92%, respectively, but still compared favourably to the sensitivity of indirect immunofluorescence which was 79% in PV and 84% in PF. All PF sera were negative in the Dsg 3 ELISA and the specificity of both assays was 98% or greater. Large numbers of samples could be analysed simultaneously over a relatively short time period. The Dsg 1 and Dsg 3 ELISAs also provided objective, quantitative, reproducible data which allowed differentiation of PV from PF and in view of these advantages, they are likely to become a routine technique in diagnostic laboratories.
Adolescent↗
Cowden's syndrome (multiple hamartoma and neoplasia syndrome): diagnostic dilemmas in three cases.
Cowden's syndrome is a multisystem disease inherited as an autosomal dominant trait with incomplete penetrance and variable expression. The disease has typical oral manifestations which often precede more systemic involvement, and the dental professional is therefore well placed to institute a regime of regular checks to ensure early treatment of any neoplasms which may occur. However, since not all of the classical signs are present in all patients, diagnosis may be difficult. The case report of a patient with most of the features of Cowden's syndrome is presented and features compared with two other possible cases.
Adult↗
Uteroglobin deficient mice-a novel animal model for IgA nephropathy?
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Animals↗
Pyostomatitis vegetans associated with asymptomatic ulcerative colitis: a case report.
Pyostomatitis vegetans, a rare pustular disorder of the oral mucosa, is a highly specific marker for inflammatory bowel disease and may be difficult to treat. A case of pyostomatitis vegetans in a patient with long-standing asymptomatic ulcerative colitis is presented. Complete remission was achieved with topical steroids; no systemic treatment was required.
Administration, Topical↗
Impaired secretory immunity in dystrophic epidermolysis bullosa.
Dystrophic epidermolysis bullosa is a congenital disorder characterized by blistering of the skin and oral mucosa. This study investigated the hypothesis that children with dystrophic epidermolysis bullosa have impaired oral secretory immunity. Immunoglobulin A (IgA), secretory IgA and IgG concentrations, and IgA and secretory IgA antibody levels to Candida albicans, Lactobacillus casei and Streptococcus mutans were measured in whole saliva from 22 children with dystrophic epidermolysis bullosa and 22 matched controls. Salivary total IgA and total IgG concentrations were significantly raised in dystrophic epidermolysis bullosa due to serum leakage from oral blistering, but the converse was seen with secretory IgA. This suggestion of a mucosal immune defect was supported by decreased secretory IgA antibody responses to all three microorganisms tested. This apparent defect in secretory immunity in dystrophic epidermolysis bullosa may be due to mucosal involvement and damage resulting in impaired antigen sampling in mucosal associated lymphoid tissue or to impaired transport of secretory IgA across the salivary gland mucosa.
Adolescent↗
Cicatricial pemphigoid: serial titres of circulating IgG and IgA antibasement membrane antibodies correlate with disease activity.
We have recently shown in a cohort of patients (n = 67) with mucous membrane pemphigoid, 63 of whom had cicatricial pemphigoid (CP), that the presence of both IgG and IgA circulating antibasement membrane zone antibodies was associated with a more severe and persistent disease. In this study we sought to ascertain whether in CP, serial titres of IgG and IgA might provide a reliable marker of disease activity. Serum titres for IgG and IgA antibodies were assayed at 6- to 12-monthly intervals in 56 patients over 32.2 +/- 20.3 (mean +/- SD) months. Antibody titres were correlated with the clinical score recorded at each follow-up visit. Sequential titres for both IgG (P < 0.001) and IgA (P = 0.015) were significantly associated with variations in disease activity. Greatest improvement was seen in patients with the greatest change in either IgG or IgA antibody titre. We suggest that serial antibody titres may therefore be useful in the assessment and management of CP.
Adult↗
Paraneoplastic cicatricial pemphigoid.
We report a 39-year-old woman with antiepiligrin cicatricial pemphigoid (CP) in association with non-small cell carcinoma of the lung. At presentation, mucosal lesions showed minimal response to combined systemic immunosuppressive agents. Following the diagnosis of non-small cell lung carcinoma and subsequent treatment with gemcitabine (a second-line chemotherapeutic agent), a significant reduction in both tumour mass and mucosal blistering was observed. Metastatic disease was subsequently associated with recurrent oral erosions. We believe this patient represents the first reported case of paraneoplastic CP.
Adult↗
In vivo analysis of secreted aspartyl proteinase expression in human oral candidiasis.
Secreted aspartyl proteinases are putative virulence factors in Candida infections. Candida albicans possesses at least nine members of a SAP gene family, all of which have been sequenced. Although the expression of the SAP genes has been extensively characterized under laboratory growth conditions, no studies have analyzed in detail the in vivo expression of these proteinases in human oral colonization and infection. We have developed a reliable and sensitive procedure to detect C. albicans mRNA from whole saliva of patients with oral C. albicans infection and those with asymptomatic Candida carriage. The reverse transcription-PCR protocol was used to determine which of the SAP1 to SAP7 genes are expressed by C. albicans during colonization and infection of the oral cavity. SAP2 and the SAP4 to SAP6 subfamily were the predominant proteinase genes expressed in the oral cavities of both Candida carriers and patients with oral candidiasis; SAP4, SAP5, or SAP6 mRNA was detected in all subjects. SAP1 and SAP3 transcripts were observed only in patients with oral candidiasis. SAP7 mRNA expression, which has never been demonstrated under laboratory conditions, was detected in several of the patient samples. All seven SAP genes were simultaneously expressed in some patients with oral candidiasis. This is the first detailed study showing that the SAP gene family is expressed by C. albicans during colonization and infection in humans and that C. albicans infection is associated with the differential expression of individual SAP genes which may be involved in the pathogenesis of oral candidiasis.
AIDS-Related Opportunistic Infections↗
Denture plaque and adherence of Candida albicans to denture-base materials in vivo and in vitro.
The aim of this paper is to review our understanding of the mechanisms and clinical significance of adhesion of C. albicans to denture-base materials in relation to denture plaque and denture-related stomatitis. Earlier reports in the literature of a 65% prevalence level of denture-related stomatitis seem to be exaggerated. More recent studies indicate that denture-related stomatitis is considerably less common, particularly in normal healthy subjects. The etiology of the condition is discussed in this review, and although much of the literature supports the view that the condition is strongly associated with C. albicans, this is not always so. In some subjects, the cause appears to be related to a non-specific plaque. This review also considers the role of denture plaque in the pathogenesis of denture-related stomatitis, the sequential development of denture plaque, and its colonization by Candida organisms. Designing controlled in vivo studies is difficult, and as a consequence, many investigators have had to resort to in vitro studies. The majority of these studies have attempted to investigate the hydrophobicity of C. albicans, relating the surface free-energy of denture-base materials, particularly acrylic resin, to that of the organism. Surprisingly little work has been directed at surface roughness and how it affects retention of organisms. Further, no attention has been paid to the properties and character of the surface, other than average surface roughness, as it affects adhesion. A comparison of results from in vitro studies on the effect on adhesion of pre-coating the surfaces of denture-base materials with saliva has produced equivocal conclusions. This is largely due to little standardization of experimental protocols between studies, particularly in the collection and handling of the saliva used. In conclusion, the review strongly supports the suggestion that adherence of C. albicans to denture-base materials in vitro is related to the hydrophobicity of the organism. The clinical significance of the observation and the mechanisms for the development and maturation of denture plaque are yet to be understood. There is a clear need for further investigation of other factors that may moderate the adhesion of organisms and subsequent colonization of denture-base materials.
Acrylic Resins↗
Adherence of Candida albicans to denture-base materials with different surface finishes.
OBJECTIVES: To assess the in vitro adherence of Candida albicans to heat-cured hard and soft denture-base materials with varying surface roughness, and to observe the effect of a mixed salivary pellicle on candidal adhesion to these surfaces. METHODS: In vitro adhesion assays on heat-cured acrylic resin (Trevalon), Molloplast B and Novus using the type strain of C. albicans (NCPF 3153A). Surfaces for the assays were prepared using clinically appropriate rotary instruments. Unstimulated, pooled and clarified whole saliva was used to assess its effect on adhesion. RESULTS: Significantly greater adhesion of C. albicans to rough rather than smooth surfaces was found (P < 0.001), as well as increased adhesion to the machined soft lining materials compared with acrylic. Pre-coating denture-base materials with saliva reduced candidal adhesion on all materials. CONCLUSIONS: Rough surfaces on denture-base materials promote the adhesion of C. albicans in vitro. However, saliva reduces adhesion of C. albicans and thus diminishes the effect of surface roughness and free surface energy differences between materials.
Acrylic Resins↗
Mucous membrane pemphigoid: a dual circulating antibody response with IgG and IgA signifies a more severe and persistent disease.
Mucous membrane pemphigoid (MMP) is an autoimmune blistering disease frequently associated with scarring of involved clinical sites. At present, therapeutic intervention in the form of immunomodulating or immunosuppressive agents is often reserved until the onset of significant inflammation and/or early cicatrization. We have therefore studied the clinical and immunopathological findings in 67 patients with MMP in order to try to establish a reliable prognostic indicator by which patients at high risk may be identified early in the disease. Inclusion criteria were a predominantly mucosal disease and the detection of IgG and/or C3 anti-basement membrane zone (BMZ) immunoreactants using immunofluorescence techniques. Patients were allocated to three disease subgroups on the basis of the modality and duration of therapeutic intervention required to achieve effective control of disease. In addition, at presentation and at each follow-up visit, a clinical score for severity of involved clinical sites was awarded and serum collected for indirect immunofluorescence (IIF). A dual circulating anti-basement membrane zone (anti-BMZ) antibody response with IgG and IgA was significantly associated with a more severe and persistent disease profile (P < 0.001). The odds ratios for requiring systemic therapy were: 11.6 among patients in whom there was a clinical score > or = 5 compared with a score < 5, and 31.3 and 66.9 among patients with IgG alone and both IgG and IgA, respectively, compared with negative IIF. The findings suggest that an assessment based upon a combination of site severity score and the presence of circulating IgG and IgA by IIF using 1 mol/L salt-split human skin substrate may be considered a useful prognostic indicator.
Adult↗