In clinical settings, the laboratory tests or any diagnostic procedures should be performed only when they give the benefits which are out-weighted complication from that procedure; money and side effects, respectively.
We, clinicians, tend to classify the patients who have similar symptoms, signs, epidemiology, risk factors and laboratory results into groups of patients that we think that they might share similar causative factors, pathogenesis and so have the therapeutic implications or will have therapeutic implications when these more homogeneous patients are subjected to clinical trials or scientific research.
These tedious jobs of our precedent physicians have proved themselves as scientific accuracy and also gear the new discoveries for the sake of knowledge or the benefits to the humankinds. UK just cerebrate their life expectancy estimation of the new born babies nowadays to be beyond 90 years!
However, we should remember that diseases are what the human creates and they are subjected to be changed, modified, obsolete, expanded, simplified or elaborious, etc according to the knowledge and interpretation.
Back to the case of vasculitis, one of the problems in classification is we dont know exactly what is the cause or what are the minimum necessary causes for developing vasculitis. From clinical, pathological, and laboratory evidence show that clinical laboratory detection of autoantibody might play role in pathogenesis of these arrays of difficult nosological entities. (Although some are proved to be the innocent bystanders or cross reactivities with the actual culprit such as antiphospholipid antibodies) From the same sources of evidence, they show that many infectious agents may be the trigger of the diseases and molecular mimicry of the self antigen is among the famous hypothesis of the diseases.
The concepts of primary vasculitis and secondary vasculitis (as elsewhere disease entities) will be ended up with less and less primary disease when the etiologic or causative agents have been recognised. In particular, in ANCA vasculitis, there are some evidences that antiMPO and antiPR3 might be some of the major players in pathogenesis of vasculitis. Recently, anti-LAMP-2 (lysosomal associated membrane protein) was found to have some pathogenetic role in ANCA-associated vasculitis. This antibody to human LAMP protein is believed to be related to fimbriated bacterial protein (although there is no prove that it really trigger the pauciimmune process.
One of the series found that more than 90% of patients with active pacui-immune FNGN have circulating anti LAMP-2 antibody while only half of patients have anti-MPO and anti-PR3 antibodies. So should the entity be considered primary and secondary? Should we abolish anti-MPO and anti-PR3 tests? Should we test anti-LAMP-2 for all ANCA associated vascultis patients instead? These questions do not have one simple answer at the moment as the sensitivity, specicificity of the tests have not been established.
Back to the topic, so in my opinion, we are in the medical school setting and we have the great opportunity to help patients to have the best case and in turn, we also have the great opportunity to learn from the patients to the very basic ground and may create some future clinical therapeutics or preventive benefits. We should encourage the learning but do not confuse the juniors (residents and fellows in training) and medical students with highly sophisticated diagnostic tests and procedures which sometimes are performed in case of research or diagnostician curiosity and sometime for epidemiological information. All the tests that are to be ordered or performed should have the goals and purposes which we should explicitly clarify and the most important thing is to overcome the curiosity of the diagnostician!
In conclusion, if I will say, I might restate to MPN is a disease entity that has been proposed recently (1994 appeared in Chapel Hill classification) there might be some benefits beyond the present therapeutic implications for differentiate between these two diseases. (Can microPAN developed to WG lately?) ANCA and anti-MPO and anti-PR3 can be used for this purpose. I will still be skeptic about anti-LAMP-2 which has not been proved so far in clinical situation but if it is possible and there is payer for this test (grant bodies), it is a good candidate for the research purpose testing to verify the hypothesis (not an established! knowledge) of the bacteria and human protein molecular mimicry. (Think about anti-DNAaseB and anti-streptolysin-O in rheumatic fever, who care!- I care.55)
In the future, this classification might be obsolete when the etiologic and treatment implications are better clarification. A good example is the classification of acute leukemia from FAB classification, not very long time before, is now evolved into the classification by cytogenetics and prognosis from treatment.
PS: I am not an expert in immunology, nephrology or hematology. Please use your careful thought in reading this article. Thank you.
