May genetic factors in fibromyalgia help to identify patients with differentially altered frequencies of immune cells?

Abstract

SummaryThere is common agreement that fibromyalgia (FM) is an extremely heterogeneous entity. Patients differ in their clinical symptoms, endocrine and immune parameters. In this study we evaluated endocrine and immunological features of distinct subsets of FM patients. In contrast to previous attempts to identify subsets of FM patients, based solely on their psychological and cognitive features, herein we propose to separate FM patients by genetic features. Allelic expression of the polymorphic promoter region of the serotonin transporter (5-HTTLPR) was analysed as a relevant genetic factor for FM. Seventy-five patients meeting the American College of Rheumatology criteria and 27 healthy age-matched controls participated in this study. All controls and FM patients were submitted to genotyping of 5-HTTLPR. Twenty-seven FM patients, who were able to discontinue hypnotic, sedative or psychotropic prescription medications for at least 2 weeks, were then subdivided into L (homozygote LL) or S groups (genotypes LS and SS). They were evaluated for salivary cortisol levels, absolute number of leucocyte subpopulations, including natural killer (NK) cells and activated T and B lymphocytes. Both groups presented decreased cortisol levels, more intense in the L group, increased all B lymphocytes subsets and reduced CD4 + CD25 high T lymphocytes. The L group had increased CD4 + CD25 low activated T lymphocytes, while the S group displayed elevated CD4 + human leucocyte antigen D-related (HLA-DR) + activated T lymphocytes and decreased NK cells. We demonstrate that genetic factors may help to identify FM individuals with differentially altered frequencies of immune cells.

Clinical profile of patients with fibromyalgia syndrome

“…The origin of the pain in FM has not been completely clear and a series of hypotheses try to explain this phenomenon. The main hypotheses involves: alteration in the ways of transmission of pain (17,18), alterations in the levels of neurotransmitters (12,19) and or biomarkers of the inflammatory process (20,21). It becomes necessary to emphasize that the presence of pain may interfere on the manifestation of other symptoms, as well as the perception may be empowered in the presence of such symptoms (22).…”

Fibromialgia: diagnóstico, fisiopatologia e tratamentos

“…Contudo, as alterações em apenas um desses fatores, não explicaria a diversidade de sintomas presentes na FM. Desse modo, acredita-se que a manifestação e evolução dessa condição são dependentes da interação entre os múltiplos fatores mencionados (CARVALHO et al, 2008).…”

“…Distúrbios neuroendócrinos como alterações nos níveis de cortisol e/ou de melatonina, parecem estar envolvidos na fisiopatologia da FM (CARVALHO et al, 2008;PERNAMBUCO et al, 2014). Dentre essas hipóteses, se destacam as que apontam para níveis reduzidos de cortisol entre pacientes com FM (CARVALHO et al, 2008).…”

“…Dentre essas hipóteses, se destacam as que apontam para níveis reduzidos de cortisol entre pacientes com FM (CARVALHO et al, 2008). Essa alteração estaria relacionada a uma disfunção do eixo hipotálamo -pituitária -adrenal (HPA), também conhecido como eixo de resposta ao estresse.…”

“…Esse eixo neuroendócrino participa da manutenção da homeostase corporal, mas sempre que o organismo se depara com um agente estressor de qualquer natureza (físico ou psicoemocional), o eixo HPA entra em hiperatividade o que resulta em níveis elevados de liberação de cortisol (CROFFORD et al, 2004). A resposta ao estresse deve ser rápida e durar de segundos a poucas horas, mas no caso de permanência do estímulo estressor por vários dias, meses ou anos, o eixo HPA entra em exaustão o que poderia explicar os baixos níveis de cortisol presentes em pacientes com FM (CARVALHO et al, 2008;TAK et al, 2011). O cortisol possui diversas ações, como a mobilização de energia estocada em depósitos corporais para ser utilizada pelas células e a ativação de osteoclastos.…”