Connective-tissue disorders, also referred to as collagen-vascular disorders, cause a variety of generalized clinical findings and are characterized by autoantibody-mediated connective-tissue abnormalities. These are also called immune-complex diseases because many involve deposition of immune complexes in specific organ or tissue sites. Some of these disorders are characterized by sterile inflammation, especially of the skin, joints, blood vessels, and kidneys, and are referred to as rheumatic diseases. For inexplicable reasons, many rheumatic diseases primarily affect women. Another major category of connective-tissue diseases includes inherited disorders of bone, skin, cartilage, blood vessels, and basement membranes. Examples include Marfan syndrome, osteogenesis imperfecta, and Ehlers-Danlos syndrome.
Relative to future pregnancies, hemopoietic stem-cell transplantation is becoming accepted therapy for severe autoimmune diseases that include systemic lupus erythematosus, systemic sclerosis, rheumatoid arthritis, and vasculitis. According to Marmont (2008), randomized clinical trials have been launched by the European Group of Blood and Marrow Transplantation (EBMT). At this time, however, even tentative conclusions are not yet available.
Although the pathogenesis has not been elucidated, immune-mediated disorders can be separated into those clearly associated with and those without autoantibody formation. So-called rheumatoid factor is an autoantibody found in many autoimmune inflammatory conditions. Those associated with rheumatoid factor include systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis (scleroderma), mixed connective-tissue disease, dermatomyositis, polymyositis, and a variety of vasculitis syndromes. In contrast, the seronegative spondyloarthropathies do not display rheumatoid factor, but are strongly associated with the presence of the HLA-B27 antigen (Benjamin and Parham, 1992; Moll, 1994). These include ankylosing spondylitis, psoriatic arthritis, Reiter disease, and likely the arthritis syndromes associated with ulcerative colitis and Crohn disease.
Because renal involvement is common and often adversely affects pregnancy, a search for coexisting renal involvement is paramount. Hypertension likewise is common, and exacerbation during pregnancy frequently forces early delivery (Wolfberg and colleagues, 2004). In some of these immune-mediated diseases, antiphospholipid antibodies are formed that can cause injury to maternal vasculature and to the placenta.
The immune system is designed to protect cells, tissues, and organs perceived as self, and to attack and destroy foreign or nonself antigenic material by the production of antibodies. This protection has two phases. The first is the innate phase, which is broad and rapid and is mediated through neutrophils, macrophages, and complement. The second is the adaptive phase, which is precise and is caused by antigen-specific reactions through T and B lymphocytes that result in memory for future exposures (Parkin and Cohen, 2001).
For some as yet unknown reason, the immune system may be stimulated to begin producing antibodies directed against self or normal tissues. These “misdirected” antibodies are called autoantibodies. The stimulus responsible for their production is unknown, but may be due to bacterial or viral injury to genetically susceptible tissues.
Autoantibodies induce destruction by at least two ...