Basic principles of the immune system and autoimmunity

The immune system is composed of two closely collaborative systems, an innate and an adaptive system. The innate immune system is a constitutive present system that can act rapidly to eradicate microbes. The primary cells of the innate immune system are macrophages, granulocytes, natural killer cells and dendritic cells. The adaptive system can be divided in a humoral and cellular response. The humoral response is characterized by activation of B-lymphocytes with subsequent maturation into plasma cells and production of antibodies, whereas a cellular immune response is characterized by transformation of T-lymphocytes into cytotoxic T-cells, capable of killing virally infected cells. Auto-reactive B- and T-lymphocytes can induce autoimmune diseases. Autoimmune blistering diseases are the result of type II hypersensitivity, e.g. autoantibodies are directed against cell or matrix components. In pemphigoid diseases antibodies are directed against hemidesmosomal components, whereas pemphigus is characterized by antibodies against desmosomal proteins.</p

Indirect immunofluorescence microscopy

The purpose of indirect immunofluorescence microscopy is to detect circulating antibodies in patient's serum. For this purpose an adequate substrate is necessary to visualize these antibodies. Monkey esophagus is the most widely used substrate for detecting of circulating autoantibodies in patients with autoimmune blistering diseases. In all variants of pemphigus antibodies show an epithelial cell surface pattern, resulting from present autoantibodies against the desmosomal molecules desmoglein 1 and/or 3. This pattern is also called chicken wire or honeycomb pattern. In pemphigoid a linear deposition along the epithelial basement membrane can be observed, caused by autoantibodies against hemidesmosomes or their connecting proteins underneath. Human salt split skin is a valuable substrate in the diagnosis of subepidermal autoimmune blistering diseases. Important antigens in the roof of salt split skin are type XVII collagen (BP180) and BP230, whereas laminin 332, p200 and type IV collagen are situated in the floor of the blister. This implies that bullous pemphigoid, mucous membrane pemphigoid, pemphigoid gestationis, and lichen planus pemphigoides show staining of IgG on the epidermal side of the blister. On the other hand anti-laminin 332 pemphigoid, anti-p200 pemphigoid, epidermolysis bullosa acquisita, and bullous SLE show staining on the dermal side. Other less used, but valuable substrates in some instances, are rat bladder and knock-out skin.</p

Direct immunofluorescence microscopy

Direct immunofluorescence plays an important role in the diagnosis of autoimmune blistering diseases. The purpose of direct immunofluorescence microscopy is to detect in vivo antibodies in patient's skin or mucosa. Direct immunofluorescence of pemphigus shows depositions of immunoglobulins and/or complement on the epithelial cell surface of keratinocytes, whereas pemphigoid shows linear deposition of immunoglobulins along the epidermal basement membrane zone. This linear deposition can be separated in an n-serrated pattern and a u-serrated pattern. An n-serrated pattern is seen in blistering diseases with binding above the lamina densa with antibodies against hemidesmosomal components, e.g. bullous pemphigoid, while a u-serrated pattern points to a sublamina densa binding diseases caused by autoantibodies against type VII collagen, e.g. epidermolysis bullosa acquisita. Finally, dermatitis herpetiformis shows a granular IgA deposition along the epidermal basement membrane zone.</p

How to take a biopsy

The skin is an organ that is easy to access for microscopy. Sections of the skin may reveal the split level of the blister, the type and distribution of inflammatory cells, and the presence, class and distribution pattern of autoantibodies. A biopsy should be taken from a location with smallest change of sample error, and the specimen specially fixated and transported for the requested microscopic techniques. Taking biopsies is the area of expertise of the dermatologist, even taking conjunctiva biopsies for immunofluorescence (IF) is possible in cases of suspicion of an autoimmune blistering disease of the eye.</p

Non-bullous Lichen Planus Pemphigoides:A Case Report

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Treatment of subcutaneous nodules after infusion of apomorphine:a biopsy-controlled study comparing 4 frequently used therapies

This study aimed to provide clinical evidence for existing treatments of subcutaneous nodules after subcutaneous infusion of apomorphine, using a biopsy-controlled prospective crossover design of four treatments. We demonstrated that dilution of apomorphine significantly improved patient satisfaction, while subcutaneous hydrocortisone reduced nodule size, however with no differences in the histopathology