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Systemic Lupus Erythematosus

Lupus consists of multiple diseases under one heading with multiple manifestations, and to compare a group that has nephritis, exclusively nephritis, to a group that has exclusively CNS disease may not be justified. Are laboratory serologies useful in the assessment of lupus? Why measuring serological parameters in patients with lupus? Well, what we actually want is to have parameters that directly reflect the pathophysiology of the disease. Because this would enable us to follow the disease process and its origin and give us the opportunity to see changes at the earliest time in order to come to intervention. Now what do we know? Lupus is a disease of autoantibodies.

Now let’s first mainly concentrate on the anti-double stranded DNA antibodies in relation to relapses of lupus. The data are disturbing in the literature. They are not in concordance. But I would like to show you one of our previous studies that we have performed in a cohort of patients with lupus, 72 patients defined based on ACR criteria, and those patients were followed for a median time of 18 ½ months. And we took monthly plasma samples from those patients.

Now what about these sort of relapses? Well, we dissected relapses in renal and non-renal relapses and as you see, particularly the renal relapses, 12 out of 13 were preceded by a significant rise in the antibodies as measured in the Farr assay. The time period between the occurrence of a significant rise in antibodies and the occurrence of a relapse was 10 weeks for the Farr assay.

Now, what can we say about the specificity of those rises? Let’s concentrate on the Farr assay. We observed during that observation period 28 rises in antibodies to double-stranded DNA as measured by Farr assay. And 23 out of those rises were indeed followed by a relapse. So we ended with these five rises in antibodies to double-stranded DNA.

Now what about the complement components? Well, first let me say, what actually causes the increase in antibodies to double-stranded DNA? Well, unfortunately we don’t know. But what we observed was that the rise in antibodies was rather specific for double-stranded DNA because it was, only in a few cases, accompanied by an increase in antibodies to an irrelevant antigen-like, or by an increase in the total level of IgG or IgM. Now how to explain the discrepancies of this study.

What we next did when we evaluated those samples in which we observed an increase in levels of anti-DNA, in one assay with the previous samples in order to be sure that we detected a real increase in anti-bodies to double-stranded DNA. We used pretty fine definitions of flares, minor or major flare. Now, what about the complement components?

Now what about other antibodies that seem to more specific, or pathophysiologic, for renal disease. Well, let me give you one example. Antibodies to C1q. Those antibodies were present in 14 out of 17 relapses with renal disease, and in 6 out of 16 with non-renal disease. And incidentally, in patients with inactive disease. Then out of 14 cases that were characterized by an increase in those antibodies prior to the relapse. So there seems to be less sensitive for detecting relapses, even renal relapses.

What about other measurements that reflect immune activation in lupus. Here I show, just as an example, the value of measuring soluble interleukin-2 receptors. In another study we observed that in 16 out of 21 relapses a rise in levels of those receptors preceded the relapse, for a median of 3.5 weeks before the relapse. And 3 out of 5 of those rises were in cases.

Yes, I would like to make two comments. The first comment is; I think that when you have a patient in your clinic, the outpatient clinic, who shows signs of lupus activity it probably is not difficult - although you have to differentiate, probably, from other possibilities, other causes - that these patients have active lupus. When I have a patient with severe proteinuria.

The second point is this; that when you are evaluating all those studies, I have mentioned already the time-frame, how frequently do you measure antibodies. Otherwise it is very important to be sure of the variability of the assays that you use. So in order to come to a conclusion you have to be sure, indeed, that there is not a large inter-assay, or even intra-assay, variability in the tests.