What About Lupus

First described in the early 1800s, lupus is a complex disease affecting women more than men and often more than one member of a family. Two things probably play a part in the emergence of this disease in patients:

genetics
an environmental trigger

Genetic Factors
Some patients have a strong genetic predisposition to lupus and need very little environmental stimulation to initiate the diseas, while others with a very slight genetic predisposition need significant stimulation from an outside source before developing the disease. The greater the degree and number of abnormalities (genetics) and stimulants (environmental) the greater the probability of developing the disease.

Close, healthy family members of lupus patients have been found to have abnormal serology (labs) for ANA (50%), rheumatoid factor (33%), anti-DNA antibodies, and antihistone antibodies (>60%) which may induce the LE cell phenomenon found only in lupus. Antihistone antibodies are seldom found in other autoimmune diseases. These serologic abnormalities are found more frequently in female relatives of lupus patients than in males.

Environmental Factors
An environmental stimulus could tip the balance between wellness and lupus.

That stimulus could be an infection; a food, plant or chemical allergy or an emotional stress. More than one mechanism may play a role in a single patient, and the process resulting in disease may differ from one patient to another - a kind of "multi hit" process.

Lupus patients seem to have greater stimulation of B cells than healthy individuals. B cells produce antibodies. An antibody is an immunoglobulin molecule (Ig) with a specific amino acid sequence on its surface which enables it to target a specific antigen (toxin). In lupus, the B cells seem to be abnormal, able to create larger than normal amounts of antibody. The greater the stimulus to B cells, the greater the risk of developing disease or experiencing a disease flare. As the B cells are stimulated, the body can be overwhelmed, and under unusual circumstances, produce auto-antibodies (antibodies against normal tissue) which could result in disease.

Overproduction of these autoantibodies can lead to inflammation in the kidneys and other vital organs.

What accounts for this development of autoantibodies in lupus patients Steinberg (Clin Immunology & Immunopathology, 1992) feels many B cells with a receptor for a self-antigen may be stimulated by something in the host, ultimately becoming overwhelmed by the higher and higher affinity of these autoantibodies for normal tissue.

Once the ability to distinguish self from foreign or non-self is compromised, lupus patients produce different spectra of autoantibodies based on:

genetic makeup
antigenic exposure
random processes

Three kinds of cells are involved in the basic immune response to a foreign substance:

magrophages
helper T cells
B cells

The macrophages (large white blood cells) are the first to encounter the foreign substance. After identifying the substance as foreign, the macrophage displays a fragment of the foreign substance (antigen) on its surface. This antigen is recognized by the helper T cell to which it binds much the same way a specific key fits into a specific lock.

Through the production of chemicals called lymphokines, the T cell sends a chemical message which activates the B cells who are programmed to attack that specific pathogen (antigen). The B cell produces quantities of antibodies (immunoglobulins-Ig). Together, these actions form the coordinated attack against a specific pathogen (antigen).

Abnormalities & Organisms Cytokines, the immune system's chemical messengers, stimulate B cell activity and are candidates for genetic defects which could predispose to lupus.

Some organisms can infect cells and interfere with their normal activities and responses. For example, the Epstein-Barr virus can infect human B cells preventing them from natural cell death (apotopsis). It can also protect T cells, programmed to attack normal tissues, from being killed before they leave the thymus gland where they mature.

In 1995, Gilkeson et al found immune cell abnormalities to dsDNA which were unique to lupus patients. The DNA from some bacterial species elicits a normal IgG response in normal patients whose immune systems recognize the bacterial DNA as foreign. In lupus patients, because of abnormal B cells, such exposure to bacterial dsDNA would stimulate an autoimmune response against normal tissues. Lupus patients have abnormalities in the clearance of bacteria and other organisms; therefore it is possible some microbes may induce disease activity.

In 1992, Ginsburg et al found Mycoplasma hominis and Ureaplasma urealyticum in 63% of lupus patients tested. These organisms have been shown to cause lupus-like symptoms, including B cell activation and the production of autoantibodies. Infection with this genitourinary form of mycoplasma can become systemic and become a persistent source of antigen.

Parvovirus has been shown to mimic lupus symptoms such as malar rash, fever, and arthritis with joint involvement, fatigue and positive ANA labs.

References

AD Steinberg, Concepts of Pathogenesis of Systemic Lupus Erythematosus, Clin Immu & Immunopath, 63:1; 4/1992, 19-22.

WE Levinson, E Jawetz, Medical Microbiology & Immunology, 3rd ed, 1994.

GS Gilkeson, AMM Pippen, DS Pisetsky, Induction of Cross-Reactive Anti-dsDNA Antibodies in Preautoimmune NZB/NZW Mice by Immunization with Bacterial DNA, J Clin Invest, 1995, 95:3, 1398-1402.

KS Ginsburg, RB Knudson, CW Walter, PH Schur, Urealplasma urealyticum and Mycoplasma hominis in Women with Systemic Lupus Erythematosis, Arth & Rhu, 1992, 35:4, 429-433.

G Nesher, TG Osborn, TL Moore, Parvovirus Infection Mimicking Systemic Lupus Erythematosus, Sem in Arth & Rhu, 1995; 24:5, 297-303.

Y Shoenfeld, G Segol, O Segol, B neary, A Klajman, BD Stollar, DA Isenberg, Detection of Antibodies to Total Histones and Their Subfractions in SLE and Their Asymptomatic Relatives, Arth & Rhu, 1987, 30:2, 169-175.