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Biomedical subjects

R W Plunkett

Publications and source records attributed to R W Plunkett.

10 recordsLinked to original sources

IgG4 as the predominant IgG subclass in pemphigoides gestationis.

BACKGROUND: Pemphigoides gestationis (PG) is a blistering disorder of pregnancy caused by antibodies against basement membrane proteins. They are directed against the 180 kD bullous pemphigoid antigen (BPAg2), towards the epitopes within the NC 16A domain. There are many similarities between pemphigoid gestationis and bullous pemphigoid (BP), but the literature so far indicated different immunofluorescence results in regards with C3 and IgG, and IgG subclasses (IgG4 vs. IgG1). METHODS: We evaluated staining patterns and IgG subclasses, as well as C5b-9 membrane attack complex (MAC) in 10 pregnant patients with PG, using sandwich double antibody immunofluorescence (SDAI) and direct immunofluorescence (DIF). RESULTS: All ten specimens stained with C3 by DIF, but only five had trace amount of IgG reactants by this method. By SDAI, 100% were positive for the IgG4 and C5b-9 MAC, 70% for IgG2, 50% for IgG1, and 40% for IgG3. CONCLUSION: IgG4 was the predominant IgG subtype identified. This finding has not been reported for PG, but it mimics results reported for BP. One explanation is prolonged disease course, as well as blocking of antigenic domains by IgG4. Understanding this completely will help develop therapies and prevention strategies for immunobullous and other autoimmune diseases, and perhaps aid in an exact classification.

Complement Membrane Attack Complex↗

Complement-fixing properties of antinuclear antibodies distinguish drug-induced lupus from systemic lupus erythematosus.

The immunofluorescence antinuclear antibody (ANA) test has been widely used to monitor autoimmune disease, but its value for diagnostic purposes is compromised by low specificity and high prevalence in disease-free individuals. The capacity of autoantibodies to fix serum complement proteins when bound to antigen is an important effector function because this property is associated with acute and chronic inflammatory processes. The current study evaluates the complement-fixing properties of antinuclear antibodies (CANA) in three well-defined and clinically-related patient groups: systemic lupus erythematosus (SLE), drug-induced lupus (DIL) and drug-induced autoimmunity (DIA). Of 20 patients diagnosed with SLE, 90% displayed complement-fixing ANA while this feature was present in only two of 18 patients with DIL and no patients with DIA without associated disease even though the mean ANA titres were similar among these patient groups. CANA was significantly correlated with anti-Sm activity. Because SLE but not DIL or DIA can be a life-threatening disease associated with complement consumption in vivo, these results demonstrate that measurement of CANA is a diagnostically useful tool and may have immunopathologic implications.

Adolescent↗

Simultaneous presence of mucous membrane pemphigoid and pemphigus vulgaris: molecular characterization of both autoantibodies.

There are several reports in the literature describing the coexistence of features of pemphigus vulgaris and pemphigoid in the same patient. We describe 15 patients with clinical, histological, and immunopathological features of mucous membrane (cicatricial) pemphigoid at the time of initial diagnosis. All 15 patients failed to respond clinically to conventional systemic agents over a mean period of 7.2 years. Hence, IVIg therapy was used. Prior to initiating IVIg therapy, features of mucous membrane pemphigoid and pemphigus vulgaris were demonstrated by various serological tests. Different assays were performed to identify molecular characteristics of these two autoantibodies. Twenty-five healthy normal individuals, 22 patients with mucous membrane pemphigoid, 17 patients with pemphigus vulgaris, and 12 patients with pemphigus foliaceus served as controls for comparison of serological studies. On indirect immunofluorescence, using monkey esophagous as substrate, sera of all 15 patients had demonstrable levels of anti-intercellular cement substance (ICS) or anti-keratinocyte cell surface antibody. Sera of 14 patients on salt split skin bound to the epidermal side of the split, which was consistent with mucous membrane pemphigoid. Sera of all 15 patients demonstrated binding to a 205-kDa protein (human B4 integrin) and a 130-kDa protein (desmoglein 3) on immunoblot. In a sample of sera from each of the 6 patients with mucous membrane pemphigoid and pemphigus vulgaris, the anti-ICS antibody was of the IgG4 subclass. The IgG4 subclass is a characteristic feature associated with pathogenic autoantibodies in pemphigus vulgaris. Hence, in such patients, a dual diagnosis should be considered and confirmed by various serological assays. It is possible that the presence of two pathogenic autoantibodies in these patients could have contributed to the lack of response to conventional immunosuppressive therapy.

Aged↗

Linear IgA bullous dermatosis in one of two piroxicam-induced eruptions: a distinct direct immunofluorescence trend revealed by the literature.

BACKGROUND: The report focuses first on two patients with piroxicam-induced bullous eruption, one whose disease was diagnosed as linear IgA bullous dermatosis (LABD) and the other with no disease-specific immunologic findings using immunofluorescence methods. A review of the literature points to a distinctive direct immunofluorescence feature of drug-induced LABD cases. OBJECTIVE: Our purposes were to focus on divergent piroxicam reactions and to compare immunofluorescence findings in our and other reported drug-induced LABD cases to randomly occurring LABD cases. METHODS: Direct and indirect immunofluorescence methods were used to study biopsy and serum samples from both cases and biopsy specimens of 40 other LABD cases. RESULTS: Tense blisters developed in two patients medicated with piroxicam. Immunofluorescence studies demonstrated deposits of IgA at the basement membrane zone (BMZ) in case 1 and only non-disease-specific fibrin deposits at the BMZ in case 2. Within 1 month of discontinuation of piroxicam, all lesions were gone in both patients. CONCLUSION: In LABD cases proven by direct immunofluorescence, (1) the index of suspicion of drug induction should be higher in cases with only IgA and no IgG in the BMZ; (2) possibly up to two thirds of all LABD cases may be drug induced; and (3) the negative immunofluorescence findings in case 2 and other cases reported in the literature suggest that LABD is one of several host responses in drug-induced blistering diseases.

Aged↗

A case of dermatitis herpetiformis with IgA endomysial antibodies but negative direct immunofluorescent findings.

A patient with clinical findings of dermatitis herpetiformis (DH), negative direct immunofluorescent (DIF) findings for junctional IgA deposits in 2 biopsy specimens, and positive for IgA endomysial (AEmA) and tissue transglutaminase (tTG) antibodies responded initially to dapsone. After dapsone had to be discontinued because of side effects, a gluten-free diet and supportive therapy controlled the disease; the AEmA and tTG antibodies became negative. Our data on 10 consecutive DH cases examined by DIF and by serum studies for AEmA and antibodies to tTG, point to frequencies of 90% DIF positive and 70% AEmA and tTG positive cases. The use of both DIF and serum tests for AEmA and tTG reveals DH cases not detected by DIF alone that respond to gluten-free diet. Findings on autoantibodies to tTG, an enzyme that metabolizes gliadin, points to a role of tTG in the immunopathology of gluten-sensitive enteropathy and helps to explain the need for a gluten-free diet in the management of DH cases.

Autoantibodies↗

The inhibitory properties of group A and B non-secretor saliva.

The existence of some form of specifically active A or B blood group substance in the saliva of group A1, A2 and B non-secretors was demonstrated. Significant inhibition of agglutination results were obtained when the salivas of these non-secretors were examined in a test procedure using anti-A + B (group O) serum and group AX red cells. Native saliva specimens from group A1, A2 and B secretors and non-secretors were filtered on Sephadex G-200 columns. The eluates were tested for blood group activity by inhibition of agglutination and for relative carbohydrate and protein content. A main excluded glycoprotein, blood group-active fraction was detected in all samples of saliva examined.

ABO Blood-Group System↗

Agglutination of group Ax erythrocytes by anti-A sera (group B).

Four random examples of group Ax erythrocytes were tested with anti-A sera (group B). Microscopic examination demonstrated a high incidence of reactivity of these cells with the anti-A sera (group B) obtained after immunization with group A substance.

ABO Blood-Group System↗

Cryopreservation of complement-coated erythrocytes.

Cells coated with complement components (C3b-C4b and C4b cells) were prepared by various methods and stored in liquid nitrogen using a low-glycerol, rapid freeze technique. Freshly coated cells, and cells coated and then frozen were tested versus various antiglobulin and anticomplement reagents to evaluate the reactivity of such frozen, stored, complement-coated human red blood cells. Liquid nitrogen preservation of such coated cells proved to be feasible when such cells were compared with freshly coated control cells.

Animals↗

Antinuclear antibodies (ANA) and complement fixing ANA in systemic connective tissue diseases.

Screening for antinuclear antibodies (ANA) with parallel tests for complement fixing ANA (C-ANA) reveal that C-ANA react either as strongly as or more strongly than ANA in most cases of systemic lupus erythematosus (SLE) and related disorders including CREST syndrome. But sera of drug induced LE and other ANA positive subjects have weak or no C-ANA. (P < 0.0005). Titrations with parallel C-ANA/ANA tests of two cases reveal primarily ANA and less C-ANA reactions in a case of drug induced LE but in CREST syndrome both ANA and C-ANA tests yield elevated titers with stronger C-ANA reactions. These findings point to distinct immunochemical mechanisms in C-ANA and ANA reactions.

Antibodies, Antinuclear↗