Immune Pathogenesis of Bullous Autoimmune Disorders

Pemphigus and pemphigoid are considered to be pro-totypic bullous disorders based on their well-characterized immune pathogenesis. Apart from pemphigus and BP, there is only circumstantial evidence that auto-reactive T cells are present and involved in the patho-genesis of the autoimmune bullous disorders epider-molysis bullosa acquisita and dermatitis herpetiformis. In PV and BP, autoreactive CD4+ T lymphocytes that are presumably crucial in initiating the autoimmune response recognize...

Psoriasis Prevalence Characteristics and Therapeutic Options

Psoriasis is one of the most common dermatological diseases. Although there is a great variation in the prevalence of psoriasis in different countries due to environmental and genetic factors, it can be said that it affects roughly 2 - 3 of the world's Caucasian population. About 20-25 of these people suffer from moderate-to-severe forms of the disease. The majority of patients with plaque psoriasis (75 ) show first signs of disease manifestation before the age of 40 years, with a peak in the...

Immunopathogenesis of Multiple Sclerosis

Cell Therapies Multiple Sclerosis

Multiple sclerosis is an immunopathological, presumably autoimmune, disease that is clearly influenced by environmental and genetic factors. The development of therapeutic strategies for MS has followed the evolution of pathogenetic concepts (Hemmer et al. 2006 Sospedra and Martin 2005 Hafler 2004), and current models of MS immunopathogenesis offer numerous molecular targets for mAb therapy (Fig. 13.1). Autoimmune T- and B-cell responses to CNS antigens are believed to drive the pathogenesis of...

Epidermolysis Bullosa Acquisita

Epidermolysis bullosa acquisita (EBA) is a rare chronic subepidermal bullous disease of the skin and mucous membranes characterized by the presence of autoanti-bodies against type VII collagen, a major component of anchoring fibrils. There is a great diversity in the clinical presentation of the disease. Generally, it can be differentiated into the mechanobullous or classic form of EBA and inflammatory variants, resembling BP, Brun- sting-Perry pemphigoid, mucous membrane pemphi-goid or linear...

Pathogenesis of Crohns Disease

Crohn Disease

Although significant advances in understanding the pathogenesis of CD have been made, there are many unknowns. CD is believed to be caused by a combination of genetic and environmental factors, affecting the mucosal immune system and culminating in an aberrant inflammatory response (Korzenik and Podolsky 2006) (Fig. 12.3). It is a polygenic disease with probable genetic heterogeneity. Some genes are associated with the disease itself, whereas others increase the risk of the disease or are...

Mode of Action

Etanercept inhibits the action of TNF by competitively binding to either TNF-a and or TNF- also known as lymphotoxin-a , thus preventing TNF from binding to endogenous receptors located on the cell surface Fig. 4.2 European Medicines Agency 2005 Enbrel US Full Prescribing Information 2006 Jarvis and Faulds 1999 . Etanercept also binds to TNF expressed on cell surface membranes cell-bound TNF Enbrel US Full Prescribing Information 2006 Jarvis and Faulds 1999 . Tumor necrosis factor-a, which...

Efalizumab Mechanism of Action

As already described, efalizumab is a humanized monoclonal antibody against CD11a, the a-subunit of LFA-1. Binding of efalizumab to CD11a leads to blockade of the interaction between LFA-1 and ICAM-1. The blockade of this interaction has several consequences Jullien et al. 2004 Fig. 5.1 , including activation of T lymphocytes in lymph nodes Inhibition of extravasation of circulating lymphocytes in inflammatory skin Blockade of T-lymphocyte re-activation in skin by APCs Reduction of the...

Rituximab in Epidermolysis Bullosa Acquisita

A recent case report described an inflammatory variant of EBA with lesions on the trunk, the hands and the oral mucosa. The patient received four courses of rituximab Fig. 8.5. Clinical response in a patient with mucosal pemphigus vulgaris PV to treatment with rituximab. The PV patient with extensive oral erosions shown here was refractory to immunosuppressive treatment including mycopheno-late mofetil 3 g day and azathioprine 1.75 mg kg day , respectively, in combination with...