HLA-B62 and HLA-DQ8 are associated with Complex Regional Pain Syndrome with fixed dystonia

Abstract

Complex Regional Pain Syndrome (CRPS) is clinically characterized by pain in combination with sensory, autonomic, and motor symptoms that may include weakness, tremor, myoclonus and dystonia of the affected limb(s). The syndrome is multifactorial in origin and mostly attributed to tissue injury. There is some evidence that the human leukocyte antigen (HLA) system plays a role in the pathophysiology of CRPS, but previous studies lacked power. Here we performed the most extensive study investigating the contribution of HLA alleles (i.e. HLA-A, HLA-B, HLA-DRB1, and HLA-DQB1) in 150 CRPS patients who also had fixed dystonia. HLA-B62 (OR=2.05 [95% CI 1.41-2.99], P=0.0005) and HLA-DQ8 (OR=1.75 [95% CI 1.20-2.57], P=0.005) were found significantly associated with CRPS and dystonia. The association remained significant after correction (HLA-B62 P(corrected) [P(c)] = 0.02 and HLA-DQ8 P(c)=0.04). The involvement of HLA-B62 and HLA-DQ8 in CRPS with dystonia may indicate that these HLA loci are implicated in the susceptibility or expression of the disease.

Systematic mutation analysis of seven dystonia genes in complex regional pain syndrome with fixed dystonia

“…Evidence for genetic factors, especially the involvement of the HLA complex on chromosome 6, in CRPS is increasing [12,27,33,46,48]. Despite these achievements, no single genetic factor has been identified in CRPS.…”

“…The syndrome may cluster in families [1,6,11,16,19,23,49]. Although several genetic associations between CRPS and the HLA gene complex on the short arm of chromosome 6 (6p21.3) have been reported [12,27,33,46,48], to date no single causative gene has been identified. In contrast to CRPS, there have been many successes in identifying genes for primary dystonia (i.e.…”

“…The age at onset of CRPS patients with dystonia is, on average, 11 years younger than that of CRPS patients without dystonia [47], which suggests a larger role for genetic factors in this more affected subgroup of patients. Notably, two studies that found a positive association with the HLA complex investigated CRPS patients with fixed dystonia [12,46]. We hypothesized that dystonia genes may confer susceptibility to CRPS or dystonia in CRPS.…”

Heart Rate Variability in Complex Regional Pain Syndrome during Rest and Mental and Orthostatic Stress

“…The pathophysiology is not known in detail, and factors such as limb immobilization, 1 ischemia with reperfusion, 2 small-fiber neuropathy, 3 neurogenic inflammation, 4 sympathetic denervation followed by supersensitivity, 5 and genetic mechanisms 6 have all been suggested to play a pathophysiologic role. CRPS is often divided into two subtypes: an acute warm and vasodilated state and a chronic cold state with vasoconstriction.…”

Infliximab Management Complex Regional Pain Syndrome

“…Relatives of patients with CRPS CRPS are more often spontaneous and at younger ages [18]; SDRC is no association between mitochondrial disorders in Young It found that some genes of major histocompatibility complex (HLA) are found more in CRPS and other less frequently; HLA-B62 and HLA-DQ8 alleles were significantly associated with CRPS [19] and TNF2 allele is most commonly found in CRPS hot phase.…”