Linear IgA Deposits Research Articles

Recent consideration on diagnosis and therapy of gingival desquamative lesions: Case report

The purpose of the studywas to present a case of desquamative gingivitis and indicate to diagnosis and therapy od desquamative lesions of gingivae. The case of desquamative gingivitis in 75 year old patient is shown. Despite pathohistological and immunofluorescent analyses having been done, the origin of the disease could not have been established at first. The undertaken therapy gave limited results. The patient did not show up for the check up for 2,5 years. When he finally came, the clinical situation was the same as the first examination. The bioptic material gave positive results. Continuous linear deposits of IgG and IgA along the basement membrane were found. The histopathological diagnosis presentes a pemphigoid. Metilprednisolon 40mg per day was prescribed, with gradual dicrease of the dose, along with tetracycline 4x250mg per day. Therapy lasted for six and a half months. Changes on the gingivae completely retreated after three months.

IgA-mediated epidermolysis bullosa acquisita: Two cases and review of the literature

We describe 2 adult patients with a subepidermal bullous dermatosis with exclusively linear IgA depositions along the epidermal basement membrane zone that were deposited in the sublamina densa zone as witnessed by direct immunoelectron microscopy. Indirect immunofluorescence microscopy of patients' sera revealed circulating IgA autoantibodies that bound exclusively to the dermal site of salt-split skin substrate. Immunoblot analysis using dermal and keratinocyte extracts were negative. Indirect immunofluorescence microscopy using type VII collagen-deficient skin (“knockout” substrate) showed no IgA binding, whereas linear IgA binding was seen at the epidermal basement membrane zone in normal human skin. The autoantigen in the patients was thus type VII collagen. A diagnosis of IgA-mediated epidermolysis bullosa acquisita (IgA-EBA) was made. We systematically reviewed the literature of this subset of patients with linear IgA dermatosis on the basis of the following criteria: exclusive binding of serum-IgA to the dermal side of salt-split skin or IgA depositions in the sublamina densa zone by indirect or direct immunoelectron microscopy. We learned that IgA-EBA is clinically indistinguishable from the classic “lamina-lucida type” linear IgA dermatosis or from the inflammatory type of IgG-mediated epidermolysis bullosa acquisita (IgG-EBA). Only a minority of the patients with IgA-EBA showed milia or scarring or had therapy-resistant ocular symptoms as in the mechanobullous type of IgG-EBA. Most patients with IgA-EBA responded to dapsone therapy. (J Am Acad Dermatol 2002;47:919-25.)

Vesiculobullous systemic lupus erythematosus: A case with circulating IgG and IgA autoantibodies to type VII collagen

We report a case of a 17-year-old Japanese boy with vesiculobullous systemic lupus erythematosus. He had a facial “butterfly” erythema and blistering eruption develop. Antinuclear, RNP, and Sm antibodies were positive. The American Rheumatism Association criteria for a diagnosis of systemic lupus erythematosus were met. A skin biopsy specimen showed papillary microabscesses of neutrophils and subepidermal blisters and deposits of IgG, IgA, IgM, and C3 by direct immunofluorescence. Indirect immunofluorescence on salt-split skin showed linear IgG, IgA, and C3 deposits on the dermal side. IgG and IgA autoantibodies in his serum reacted with the 290-kd proteins of type VII collagen from human dermal extracts and the recombinant fusion proteins from the noncollagenous domain of type VII collagen by Western immunoblot. To our knowledge, this is the first report of vesiculobullous systemic lupus erythematosus with circulating IgG and IgA autoantibodies to type VII collagen. (J Am Acad Dermatol 2002;47:S283-6.)

Esophageal cicatricial pemphigoid

A 69-year-old woman was admitted with hoarseness and dyspnea of 2 weeks' duration. Examination revealed multiple, painful oral ulcers and numerous erythematous vesiculobullous lesions on the upper trunk (A). Pulmonary function testing disclosed a moderate obstructive defect and suggested the presence of a fixed obstructive lesion. Laryngoscopy revealed edematous mucosa and multiple ulcerations in the hypopharynx with a stricture in the supraglottic region (B). Dysphagia and epigastric discomfort developed while the patient was hospitalized. At esophagoscopy, patches of erythema, whitish plaques, erosions, and sheets of sloughed mucosa were noted in the mid esophagus (C). A skin biopsy specimen disclosed infiltration of the basement membrane by inflammatory cells along with subepithelial bullae (D; H&E, orig. mag. ×40). Immunohistochemical studies disclosed linear deposits of IgG, IgA, and C3 along the basement membrane zone of the skin. After treatment with dapsone, systemic corticosteroid, and orally administered cyclophosphamide, the esophageal, oral, and skin lesions were mostly improved. However, dyspnea caused by the supraglottic stricture had worsened and a tracheostomy was performed.

False-negative results in immunoblot assay of serum IgA antibodies reactive with the 180-kDa bullous pemphigoid antigen: the importance of primary incubation temperature.

Different subepidermal autoimmune blistering skin disorders are characterized by linear deposition of IgA, sometimes accompanied by linear IgG, along the epidermal basement membrane zone. Identification of the targeted autoantigen is usually attempted by immunoblotting. Although immunoblotting works well for human IgG, the method is less successful for IgA and often no or only faint signals are obtained. To improve the method of immunoblotting for diagnosis of IgA-mediated bullous dermatoses. Eleven sera, selected from patients with linear deposition of IgA along the epidermal basement membrane zone in vivo, were tested by immunoblotting for antigen specificity using different primary incubation temperatures. No reliable information regarding IgA antigen specificity was obtained when the primary incubation was undertaken at room temperature. In 10 of 11 sera, IgA bound to the 180-kDa bullous pemphigoid antigen (BP180) when the primary incubation temperature was increased to 37 degrees C. Primary incubation at room temperature may result in false-negative results in the IgA-BP180 immunoblot assay.

SENSORINEURAL HEARING LOSS IN LINEAR IgA DISEASE

A 23-year-old female with progressive sensorineural hearing loss developed widespread blistering eruptions while under evaluation for the hearing loss. The lesions showed findings characteristic of linear IgA disease (LAD) on histochemical studies. Linear IgA disease is a dapsone responsive autoimmune subepidermal blistering disease characterised by linear IgA deposits in the basement membrane zone. The complete spectrum of this systemic disease is still not clear and this is the first report of association between LAD and sensorineural deafness.

Mapping of epitopes on the BP180 ectodomain targeted by IgA and IgG autoantibodies in patients with the lamina lucida-type of linear IgA disease.

Linear IgA disease (LAD) is an autoimmune subepidermal blistering skin disease characterized by the linear deposition of IgA at the dermoepidermal junction. Serum from patients with LAD most commonly contains autoantibodies that are directed against the hemidesmosomal transmembrane glycoprotein BP180 (type XVII collagen). Various antigenic sites on the extracellular domain of this anchoring filament protein have been shown to be targeted by autoantibodies in different autoimmune bullous skin diseases, including bullous pemphigoid and cicatricial pemphigoid (CP). However, little is known about epitopes on BP180 recognized by autoantibodies in LAD. In this study, we used three recombinant GST fusion proteins, together roughly covering the entire BP180 ectodomain, to characterize the autoimmune response in serum from patients with LAD. Interestingly, we found both IgA and IgG reactivity to all three portions of the BP180 ectodomain. The strongest reactivity was observed with the C-terminal portion of BP180. This is also the major region recognized by autoantibodies in patients with CP. This finding correlates with the observation that there may be significant overlap of the clinical and immunopathological findings in LAD and CP.

IgA nephropathy: recent developments.

IgA nephropathy (IgAN), a mesangial proliferative glomerulonephritis (GN), is the most common GN in all parts of the world where renal biopsy is widely practiced. It is unique among glomerular diseases in being defined by immunohistochemical findings, i.e., mesangial deposition of IgA, rather than by light microscopy. Because the clinical features of IgAN were discussed in 1997 (1), we focus on recent developments in IgAN. Henoch-Schonlein purpura (HSP) is an IgA-mediated systemic vasculitis in which the glomerular disease may be indistinguishable from IgAN. IgAN seems to be a kidney-restricted form of HSP. HSP is not discussed in detail here; the reader is referred to the recent review by Rai and colleagues (2). Clinical Presentation In the great majority of cases, IgAN is an isolated renal disease with no apparent clinical antecedent or association— primary IgAN. As well as the association with IgA-mediated systemic vasculitis in HSP, there are a number of other clinical contexts that seem to predispose to IgAN, usually called secondary IgAN. Among the best characterized associations are those with rheumatoid arthritis, ankylosing spondylitis, and Reiter’s syndrome; celiac disease and dermatitis herpetiformis; chronic liver disease (especially alcohol induced); and viral diseases, particularly HIV infection and hepatitis B (in endemic areas). However, caution should be exercised in interpreting some other associations as causal. There are many anecdotal reports of single cases that may reflect merely chance associations with a disease as common as IgAN. Approximately 40 to 50% of patients present with recurrent macroscopic hematuria, which usually coincides with mucosal infection or exercise. This feature is virtually never seen after the age of 40 yr. Asymptomatic hematuria with or without proteinuria is the presentation in 30 to 50% of most series. There is an “iceberg” effect in the apparent prevalence of this presentation—the extent to which only the tip of the iceberg is identified as having IgAN being decided by local attitudes toward urine testing and renal biopsy. Nephrotic syndrome is unusual, being the presentation in only 5% of all IgAN. Uncommon but well described is the coincidence of IgAN and minimal change disease in both adults and children. Acute renal insufficiency is uncommon in IgAN, occurring in only 5% of cases. It is described in association with macroscopic hematuria, although this is an infrequent clinical problem even when hematuria is heavy. Alternatively, it may be due to crescentic IgAN. To distinguish between these two clinical settings, renal biopsy is mandatory in acute renal insufficiency unless recovery of renal function is rapid. By analogy with pauci-immune crescentic nephritis, a number of investigators have sought evidence of IgA-antineutrophil cytoplasmic antibodies (ANCA) in both IgAN, particularly crescentic IgAN, and HSP. Although there are a number of cases in which IgA-ANCA seems to be associated with active disease, overall findings are inconsistent. This may in part reflect methodologic differences. However, on occasion, patients with IgAN or HSP have circulating IgG-ANCA, and in some the diagnostic criteria for microscopic polyangiitis or Wegener’s granulomatosis are met. These patients respond to immunosuppressive therapy (3). A few patients with linear capillary wall IgA deposition have also been described, presumably an IgA-mediated variant of Goodpasture syndrome (4). Approximately 10 to 20% of patients with IgAN present with established chronic renal insufficiency. It is usually assumed that these patients have long-standing disease that differs from the classic presentations only because the patient did not come early to medical attention.

Naproxen-Associated Linear IgA Bullous Dermatosis: Case Report and Review

Linear IgA bullous dermatosis (LABD) is an acquired autoimmune subepidermal blistering disorder in which linear deposits of IgA are found along the basement membrane. Idiopathic, systemic disorder-related, and drug-induced forms of LABD have been described. Drug-induced LABD occurs in association with drug administration and resolves when the offending agent is discontinued. Other forms of LABD assume a more chronic course. The nonsteroidal anti-inflammatory drugs piroxicam and diclofenac have been previously reported to induce LABD. To our knowledge, this article describes the first documented case of LABD associated with naproxen administration, which resolved after discontinuation of the drug.

Subepidermal blasenbildende Autoimmundermatose mit linearen Ablagerungen von IgA und IgG

A 29-year-old female patient with an autoimmune subepidermal blistering disease had linear deposits of both IgA and IgG at the basement membrane zone. Clinically, the patient presented with tense blisters on the face, trunk, extremities and oral mucosa. Histologically, we found a subepidermal blister formation and a predominantly neutrophilic infiltrate. Direct immunofluorescence showed linear deposits of IgA along the basement membrane zone, as well as linear deposits of IgG and C3 as typically found in bullous pemphigoid. Indirect immunofluorescence demonstrated circulating IgA and IgG autoantibodies. This case extends previous reports on a subgroup of patients with subepidermal blistering diseases characterized by the presence of both IgA and IgG anti-basement membrane antibodies. These patients reveal clinical, histological and immunopathological features of linear IgA disease and bullous pemphigoid.

Drug-induced linear IgA bullous dermatosis probably induced by furosemide

Linear IgA bullous dermatosis (LABD) is an autoimmune disease, characterized by linear deposition of IgA along the basement membrane zone. Drug-induced LABD is rare but increasing in frequency. A new case of drug-induced LABD associated with the administration of furosemide is described. (J Am Acad Dermatol 1999;41:103-5.)

The role of lymphocytes, granulocytes, mast cells and their related cytokines in lesional skin of linear IgA bullous dermatosis.

Linear IgA bullous dermatosis (LAD) is an acquired, heterogeneous, subepidermal blistering disease characterized by linear IgA deposits at the dermoepidermal basement membrane zone (BMZ), often with circulating IgA antibodies to the BMZ. The pathogenetic mechanism, possibly related to the immunophenotype of infiltrating cells, as well as the potential role of cytokines in determining bullous lesions, have not yet been elucidated. An immunohistochemical study was performed with a large panel of monoclonal antibodies [to CD3, CD4, CD8, CD25, CD1a, CD30, CD54, CD50, endothelial leucocyte adhesion molecule-1, vascular cell adhesion molecule-1, myeloperoxidase (MPO), eosinophil cationic protein EG1 and EG2, tryptase, HLA-DR, human interleukin (IL)-3, human IL-5, human IL-8, human IL-4, tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma and granulocyte/macrophage colony-stimulating factor] using the alkaline phosphatase-antialkaline phosphatase procedure on lesional and perilesional skin of nine patients (one male, eight female; age range 8 months-80 years) with clinical, histological and immunofluorescent proven LAD. The predominant infiltrating cells, distributed mostly inside and below the bullae, were neutrophils and eosinophils which showed intense activation (MPO +, EG1 +, EG2 +). The lymphocytic infiltrate, consisting principally of CD4 +, HLA-DR + and CD30 + T cells, had a predominantly perivascular distribution. Proinflammatory cytokines, such as TNF-alpha and IFN-gamma, showed a moderate focal expression on the dermal perivascular sites; IL-8 was found to have a particularly intense staining on all the epidermal cell layers and at perivascular and vascular sites. Other cytokines, such as IL-4 and IL-5, showed a prevalent intracytoplasmic staining on some cells of the dermal infiltrate (probably mastocytes and lymphocytes), and at the dermal-epidermal separation sites there was also an intense scattered distribution of IL-5. The specific tissue lesions of LAD may be the consequence of the IgA deposits at the BMZ and also of the release of these cytokines together with tissue damage enzymes derived from neutrophils or eosinophils.

Linear IgA disease associated with lymphocytic colitis

A 66-year-old woman presented with a bullous skin eruption and chronic diarrhoea. Lesional skin showed subepidermal blistering, and direct immunofluorescence of perilesional skin revealed linear deposits of IgA at the dermoepidermal junction, establishing a diagnosis of linear IgA disease (LAD). Chronic watery diarrhoea complicated by substantial loss of body weight preceded the skin eruption for several months. On endoscopy, the colon appeared macroscopically normal. On histology, the colon mucosa showed increased numbers of intraepithelial lymphocytes and infiltrates of mononuclear cells in the lamina propria, indicative of lymphocytic colitis. Treatment with methylprednisolone and dapsone led to complete clearing of the bullous skin eruption and marked improvement of the patient's diarrhoea. Gastrointestinal disorders such as lymphocytic colitis have rarely been reported in patients with LAD. Whether the simultaneous occurrence of these two diseases is coincidental or due to related pathogenetic mechanisms remains to be seen.

The localization of target antigens and autoantibodies in linear IgA disease is variable: correlation of immunogold electron microscopy and immunoblotting.

Linear IgA disease (LAD) of adults and children is a dapsone-responsive, autoimmune subepidermal blistering disease characterized by linear IgA deposits at the basement membrane zone (BMZ) of the skin and mucosa. Circulating IgA antibodies to BMZ components are often present. In this study we investigated the ultrastructural localization of the antigens and autoantibodies in six patients with LAD (five adults and one child). Using a direct postembedding immunogold electron microscopy (EM) technique, three different patterns of IgA antibody deposition were seen in the skin of four patients with LAD. The IgA deposits localized within the uppermost part of the lamina lucida and to the basal surface of the hemidesmosome in two patients, to the lamina lucida in one, and to the lamina densa in the fourth patient. Using an indirect immunogold EM technique and serum or purified blister fluid from two additional LAD patients, we showed that the serum autoantibodies of one patient bound to the hemidesmosome of the BMZ, while the autoantibodies in the blister fluid of the other patient bound to the lamina densa and sublamina densa including the anchoring fibrils in a labelling pattern similar to that of the monoclonal antibody (LH7.2) to collagen VII. All the autoantibodies binding to the hemidesmosome or lamina lucida recognized a protein in epidermal extracts of molecular weight 180 kDa or its breakdown product of 97 kDa, 200 kDa or 230 kDa. The antibodies binding to the lamina densa recognized proteins of 180 and 285 kDa. The antibodies that bound to the lamina densa and anchoring fibrils recognized collagen VII. In this immunogold EM study we have shown four patterns of IgA labelling in six patients with LAD, associated with five different antigens as recognized by immunoblotting. These results, together with our previous immunofluorescence and immunoblotting findings add support to the contention that LAD is a heterogeneous disease as regards both the target antigens and epitopes.

Depot sulfonamid associated linear IgA bullous dermatosis with erythema multiforme‐like clinical features

A case of erythema multiforme-like reaction, following therapy with sulfadimethoxynum is reported in a 19-year-old male patient. Histological examination demonstrated a subepidermal bulla and direct immunofluorescence revealed linear deposition of IgA at the dermoepidermal junction. These observations illustrate that linear IgA bullous dermatosis can mimic the clinical features of erythema multiforme and suggest the possibility of drug-induced pathogenesis.

Depot sulfonamid associated linear IgA bullous dermatosis with erythema multiforme-like clinical features

A case of erythema multiforme-like reaction, following therapy with sulfadimethoxynum is reported in a 19-year-old male patient. Histological examination demonstrated a subepidermal bulla and direct immunofluorescence revealed linear deposition of IgA at the dermoepidermal junction. These observations illustrate that linear IgA bullous dermatosis can mimic the clinical features of erythema multiforme and suggest the possibility of drug-induced pathogenesis.

Vitamin K 1–induced localized scleroderma (morphea) with linear deposition of IgA in the basement membrane zone

We describe a 45-year-old white man in whom distinctive clinical and histologic features of localized scleroderma developed at sites of injection of vitamin K 1 (phytonadione). A direct immunofluorescence test demonstrated prominent linear deposition of IgA along the basement membrane zone. No circulating antibasement membrane zone IgA antibodies were identified on indirect immunofluorescence testing. We believe that the unusual immunofluorescence finding in our patient is nonspecific and represents an epiphenomenon caused by cutaneous injury. (J Am Acad Dermatol 1998;38:322-4.)

P195 Adult vesiculobullous disease with agressive ocular involvement and linear IgA deposits

P195 Adult vesiculobullous disease with agressive ocular involvement and linear IgA deposits

Linear IgA bullous dermatosis in south India.

A study of five cases of linear IgA dermatosis (LABD) in a referral hospital in South India is presented. A dermatologic examination, skin biopsy, and direct immunofluorescence were carried out on all patients. Patients were then followed up. All five cases showed linear IgA deposits at the dermo-epidermal junction. One case in addition showed IgG and C3 deposits. All cases responded to treatment with dapsone. The treatment duration varied from 14 to 16 months and the fifth patient is still on treatment after 37 months. Linear IgA bullous dermatosis is a self-limiting bullous disorder. To the best of our knowledge this is the first report of LABD from India.

Interleukin-2 associated linear IgA bullous dermatosis

Linear IgA bullous dermatosis (LABD) in adults is characterized by subepidermal bullae associated with a linear deposition of IgA at the basement membrane zone. Its cause is unclear, although it appears to have an immune-mediated basis. The development of LABD in a cancer patient undergoing immunotherapy has been described in the French literature. We describe a similar case of LABD arising in a patient while undergoing interleukin-2 immunotherapy for renal cell carcinoma.