Elevado numero de falsos positivos en IgeneX y varias reflexiones sobre fiabilidad de pruebas y diagnósticos

[Notjustfatigue]

Buenas,

Abro este hilo porque me he quedado impresionado leyendo un artículo publicado sobre los falsos positivos en las pruebas de IgeneX y a la vez bastante preocupado de si podría haber los mismos problemas con otras pruebas tipo el Elispot (estaba pensando en hacérmelas, más que nada por una pura cuestión de satisfacción de curiosidad, dado que al estar intentado tratarnos con LDI, esto al final es lo de menos). Lo que me pone verdaderamente a temblar es la cantidad de compañerxs que se habrán puesto en larguísimos y costosísimo (tanto a nivel económico, como de salud) con terapias antibióticas:

Extraído de: "A comparison of lyme disease serologic test results from 4 laboratories in patients with persistent symptoms after antibiotic treatment." https://academic.oup.com/cid/article/59 ... logic-Test (Si alguien no lo entiende y tiene especial interés, se puede intentar traducir).


"Specialty laboratory A saw a reduction in sensitivity, while for Specialty laboratory B* sensitivity increased almost two-fold. This increase occurred when they applied their own interpretation to the WB. Thus, one could claim that their methods provided greater sensitivity. However, this increase in sensitivity came at what can only be considered an unacceptable price, a steep decrease in specificity, 15 of 40 (37.5%) of the normal healthy controls met their IgM criteria, 11 of the 40 (27.5%) met their IgG criteria and 23 of the 40 healthy controls (57.5%) met one or the other.

This study not only demonstrates that “Lyme specialty laboratories” offered no advantage but it provides a lesson in laboratory medicine. Many seem to have forgotten that like other serologic assays, Lyme serologies are not by themselves diagnostic. This raises a major issue, how should serologies be used and what is the ability of Lyme serologies to correctly predict if a person does or does not have Lyme disease. For any test, predictive value has to be considered. In the case of Lyme disease, positive predictive value refers to the ability for a positive serology to correctly identify someone with Lyme disease and negative predictive value refers to the ability for a negative serology to correctly identify someone without Lyme disease. Both of these values are directly related to the pre-test likelihood of having the disease.

But what is the meaning of a positive serology in patients with the same nonspecific complaints? There are physicians who routinely order LD serologic assays in patients primarily based on nonspecific complaints, including fatigue, stiff neck, arthralgia, myalgia, palpitations, abdominal pain, sleep disturbance, poor concentration, irritability, depression, back pain, headache, dizziness, or other nonspecific symptoms. Is there utility in doing this? All of these nonspecific symptoms are commonly reported in otherwise healthy members of the general population. With 20-25% of the population having nonspecific complaints, the positive predictive value of a positive serology using CDC criteria, IgG only for complaints of over 4 weeks, is extremely poor. It is certainly not diagnostic. For serologies with specificities like those of reported for “Lyme specialty laboratory” B, a “positive serology” in this patient population has such a low positive predictive value that it has virtually no value.

It is obvious that alternatives to current assays and the CDC criteria are needed. However, changes require rigorous scientific validation and in the absence of valid proof, “new criteria” are simply unacceptable. Nonspecific assays and serologies in patients with a low pre-test likelihood of LD are a combination that does more harm than good. High positive predictive value requires good assay specificity and a high pre-test likelihood of LD."


*El Lab B parece ser IgeneX basándose en sus criterios pubicaados sobre intepretación del WesternBlot. El criterio para resultado positivo en IgeneX son 2 de las siguientes 6 bandas: 23-25kDa, 31 kDa (Osp A), the 34 kDa (Osp B), 39 kDa, 41kDa and/or the 83-93 kDa.

Esto supone en la práctica un 57% de falsos positivos (lo cual es escalofriante).

El artículo plantea además la duda acerca de los dx. de Lyme y la instauración de ttos. acordes en pacientes con los mismos síntomas inespecíficos.

Además, otro estudio, "Laboratory Testing for Lyme Disease: Possibilities and Practicalities" https://www.ncbi.nlm.nih.gov/pmc/articles/PMC153420 indica lo siguiente:

"The numerous antigens present in whole-cell assays can result in cross-reaction with antibodies to other microorganisms or tissue components. Many diseases have been reported to cause significant cross-reactivity in IgM and/or IgG assays. Among such diseases are autoimmune disorders, Epstein-Barr virus infection, bacterial endocarditis, syphilis, other spirochetal infections, and Helicobacter pylori infection."

Vamos, que puede haber reacciones cruzadas con otros anticuerpos contra otros microorganismos o componentes tisulaes y que hay muchas patologías en las que se han encontrado numerosa rectividad cruzada en ensayos IgM y/o IgG.

Por último, Naviaux hizo la siguiente apreciación el año pasado: "https://www.omf.ngo/2016/09/09/viruses- ... ob-naviaux":

"Third, latent and reactivated viral and bacterial infections can occur, but in the case of ME/CFS that has lasted for more than 6 months, this may be the exception rather than the rule. Some doctors and scientists have not done a good job at educating patients and other scientists about the difference between serological evidence of infection in the form of antibodies like IgM and IgG, and physical evidence of viral replication like PCR amplification of viral RNA or DNA, or bacterial DNA."


Lo que viene a decir es que las reactivaciones infecciosas virales y bacterianas pueden ocrurrir, pero en el caso del SFC aquellas que han persistido durante más de 6 meses son más la excepción que la regla y que algunos doctores y científicos no han hecho un buen trabajo educando a los pacientes y otros científcos sobre la diferencia entre la evidencia serológica de una infección en forma de anticuerpos como las IgM y las igM y las evidencias físicas de replicación como amplificaciones PCR de ADN o ARN viral o ADN bacteriano.


Cuando creo tener más claras las cosas, de pronto hay algo que me hacer dejar de verlas claras....En fin....esperemos que todos los rumores que apuntan a varias publicaciones al respecto entre finales de verano y finales de año tanto por parte de la OMF, como por otras, acaben de arrojar luz a todo este asunto.