At this time of year, patients with lupus, rheumatoid arthritis, and other autoimmune diseases always ask, "Should I get a flu vaccination?" At this time in our history, many patients are also asking, "Should I get a smallpox vaccination or the H1N1 vaccination?" These questions are really about three more general questions:
The brief answers, which are different depending on the disease and vaccine, are:
Although little is known about susceptibility to smallpox, based on what happens with the related varicella virus (which causes chickenpox and shingles), patients on immunosuppressive drugs will likely be at high risk for severe disease if they are exposed to smallpox.
For both diseases, the increased risk includes patients taking: corticosteroids, such as prednisone and methylprednisolone (Medrol); immunosuppressive drugs, such as methotrexate (Rheumatrex, Trexall), azathioprine (Imuran), mycophenolate mofetil (CellCept), cyclophosphamide (Cytoxan), leflunomide (Arava), cyclosporine (Sandimmune, Neoral) and similar drugs; and biologics, such as the TNF-alpha inhibitors infliximab (Remicade) and etanercept (Enbrel) and the IL-1 inhibitor anakinra (Kineret).
However, the smallpox vaccine now is use is a live virus vaccine. This virus will spread rapidly in the bodies of patients whose immune systems are weakened by drugs or disease, and in patients with skin rashes. The currently available smallpox vaccine will be dangerous to patients with immune system disease, to those taking immunosuppressive drugs, to those with severe skin rashes, and to those whose spleens have been removed. Such patients should not receive this vaccine. (Other smallpox vaccines now in development do not contain live viral particles and may be safer, but this cannot be confirmed until clinical trials are completed.) Another important point is that the vaccination site sheds virus for up to two weeks; people in close contact with persons vaccinated, for instance family members, can become ill. Thus people living in the same house as persons with suppressed immune systems, if vaccinated, are potentially dangerous to their housemates.
The author participated on a national committee that evaluated vaccination policy in the context of terrorism. Readers can be assured that concern about vaccinating persons with chronic illness, high susceptibility, and immunosuppression, is very much on the minds of those officials who are setting immunization policy. People with AIDS, for instance, and people undergoing cancer chemotherapy or on renal dialysis are at even greater risk, and are in the community in higher numbers, than are those with lupus or rheumatoid arthritis. If and when smallpox vaccination is offered to the public at large, the rules will be well spelled out to doctors and patients about how to protect those who are especially vulnerable.
Abstract: The sera of 24 women with SLE who received influenza vaccine were tested by ELISA for anti-DNA, anticardiolipin, anti-Sm, anti-Sm/RNP, anti-Ro and anti-La. Blood samples were withdrawn at the time of vaccination and 6 and 12 weeks after vaccination. The mean age at enrolment into the study was 46.1 years. The mean disease duration was 9.1 years. SLEDAI scores were 6.6 at vaccination, 4.9 at 6 weeks and 5.1 at week 12. The vaccine was not associated with the generation of anti-DNA. At time of vaccination a single patient had anti-Sm, four patients had anti-Sm/RNP antibodies, none of the patients had anti-La antibody and six had anti-Ro antibodies. Six weeks after vaccination four, eight, nine and three patients had autoantibodies reacting with Sm, Sm/RNP, Ro and La, respectively. Twelve weeks after vaccination none of the patients had anti-Sm, three had anti-Sm/RNP, five had anti-Ro and two had anti-La antibodies. Following vaccination six and three patients developed IgG and IgM anticardiolipin antibodies, respectively. In summary, although the influenza virus vaccine is clinically safe for patients with SLE it may trigger the generation of autoantibodies. This effect is usually short term and has no clinical significance.
Abstract: Infectious agents may induce autoimmune disease through several mechanisms, notably antigen mimicry and inflammation of the target organ; conversely, infections may protect from autoimmune diseases. This paradoxical effect has been demonstrated for a number of bacteria, viruses and parasites on a variety of spontaneous or experimentally induced animal models of autoimmune diseases (e.g. experimental allergic encephalomyelitis, lupus mice, non-obese diabetic mice). The mechanisms of the protection are still ill-defined, and probably vary according to models. Stimulation of immunoregulatory CD4 T cells has been shown to play a central role in several major models. The role of superantigens is also important, like that of Toll-like receptors. Antigen competition is another major mechanism, itself open to several interpretations. Epidemiological data support a protective role of infections on human allergic and autoimmune diseases. These diseases are much more common in countries with high socio-economic development (typically Northern countries in Europe). The reason for this cannot be fully explained by genetic differences because migrating populations develop these diseases with the same incidence of the adoptive country rather than that of the country of origin. It is interesting that the frequency of these diseases has been increasing in developed countries over the last 20 years but not in undeveloped ones.
Abstract: In addition to their effects on sexual differentiation and reproduction, sex hormones influence the immune system. This results in a gender dimorphism in the immune function with females having higher immunoglobulin levels and mounting stronger immune responses following immunization or infection than males. The greater immune responsiveness in females is also evident in their increased susceptibility to autoimmune diseases. However, a clear understanding of the myriad of effects that sex hormones have on the immune system is lacking. Studies in normal mice show that estrogen treatment induces polyclonal B cell activation with increased expression of autoantibodies characteristic of autoimmune diseases. Several mechanisms appear to contribute to the break in tolerance and the increase in plasma cell activity including a reduction of the mass of the bone marrow and the thymus, the emergence of sites of extramedullary hematopoiesis and altered susceptibility of B cells to cell death. In addition, sex hormone levels in both humans and experimental models correlated with the activity of their cytokine-secreting cells indicating that sex hormones influence the cytokine milieu and suggesting that altered sex hormonal levels in autoimmune patients contribute to the skewed cytokine milieu characteristic of systemic lupus erythematosus (SLE). While sex hormones alone do not cause autoimmune disease, abnormal hormone levels may provide the stage for other factors (genetic, infectious) to trigger disease. Understanding the physiology of the interaction between sex hormones and immune function and its potential pathological consequences may provide insight into the autoimmune diseases and new directions for their treatment.