Rheumatoid Factor: A Novel Determiner in Cancer History

Abstract

The possible interplay between autoimmunity and cancer is a topic that still needs to be deeply explored. Rheumatoid factors are autoantibodies that are able to bind the constant regions (Fc) of immunoglobulins class G (IgGs). In physiological conditions, their production is a transient event aimed at contributing to the elimination of pathogens as well as limiting a redundant immune response by facilitating the clearance of antibodies and immune complexes. Their production can become persistent in case of different chronic infections or diseases, being for instance a fundamental marker for the diagnosis and prognosis of rheumatoid arthritis. Their presence is also associated with aging. Some studies highlighted how elevated levels of rheumatoid factors (RFs) in the blood of patients are correlated with an increased cancer risk, tumor recurrence, and load and with a reduced response to anti-tumor immunotherapies. In line with their physiological roles, RFs showed in different works the ability to impair in vitro anti-cancer immune responses and effector functions, suggesting their potential immunosuppressive activity in the context of tumor immunity. Thus, the aim of this review is to investigate the emerging role of RFs as determiners of cancer faith.

False-Positive Causes in Serum Cardiac Troponin Levels

“…2022;14(2):80-87 are directed against their own IgG. Elevated levels of rheumatoid factor are not only of diagnostic value, but can also have a significant impact on the results of laboratory tests performed on immunochemical analyzers [23,[40][41][42][43][44][45]. In patients with autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus, etc.…”

“…Fibrin clots Competitive interaction of fibrin clots with diagnostic antibodies [17-19, 30, 31] Heterophile antibodies Cross interaction of heterophile antibodies with anti-cTn included in the diagnostic test system [19,20,[32][33][34][35][36][37] Alkaline phosphatase Endogenous alkaline phosphatase can catalyze the enzymatic reaction in immunoassay and thereby amplify the signal, which is proportional to the concentration of cardiac troponins in the sample [3,21,22,38,39] Rheumatoid factor Nonspecific interaction of rheumatoid factor (autoantibodies) with diagnostic antibodies [3,27,33,[40][41][42][43][44][45] Cross-reactions of diagnostic (anti-cTn) antibodies with troponin molecules released from skeletal muscle Cross-reactions of diagnostic antibodies with skeletal troponin molecules released into the bloodstream during skeletal muscle injury Re-expression of cardiac troponin molecules in skeletal muscles after injury and the release of these molecules into the bloodstream from skeletal muscle fibers [47][48][49]53]…”

The Main Causes and Mechanisms of the Formation of False Positive Results of Troponin Immunotests

“…Проведенный анализ литературы позволил прийти к заключению том, что ложноположительные результаты тропониновых иммунотестов чаще всего обусловлены следующими причинами: наличием фибриновых сгустков в исследуемом образце [37][38][39][40], повышенной активностью щелочной фосфатазы [41][42][43][44], присутствием гетерофильных антител (иммуноглобулинов) [45][46][47][48][49][50][51][52] или ревматоидного фактора [53][54][55][56][57][58][59], а также перекрестными реакциями диагностических (анти-cTnT и/или анти-cTnI)…”

“…Ревматоидный фактор -аутоантитела (иммуноглобулины), которые направлены против собственных иммуноглобулинов класса G. Повышенные уровни ревматоидного фактора не только имеют диагностическую ценность [53], но и могут оказывать значимое влияние на результаты лабораторных исследований, проводимых на иммунохимических анализаторах, включая тропониновые иммунотесты. Согласно многочисленным сообщениям, у пациентов, страдающих аутоиммунными заболеваниями (системная красная волчанка, ревматоидные артриты, полимиозиты и др.…”

Autoantibodies in Rheumatoid Arthritis: Historical Background and Novel Findings

“…It encompasses immunoglobulins of IgM, IgG, and IgA classes targeting the Fc-fragment of IgG. However, RF can be present in a variety of other rheumatologic and non-rheumatologic conditions, including a broad spectrum of infectious diseases -most importantly hepatitis C-virus infection and cryoglobulinemia [48], as well as cancer [49][50][51][52]. The specificity of RF in RA is estimated to be 85% at best, and the sensitivity to be in the range between 60 and 90% [52].…”