Circulating antimyenteric autoantibodies in Tunisian patients with idiopathic achalasia

Abstract

The physiopathology of idiopathic achalasia is still unknown. The description of circulating antimyenteric autoantibodies (CAA), directed against enteric neurons in sera of patients, suggests an autoimmune process. Recent data showed controversies according to the existence and the significance of CAA. The aims of this study were to investigate whether CAA are detected in Tunisian patients with idiopathic achalasia and to look for associated clinical or manometrical factors with CAA positivity. Twenty-seven patients with idiopathic achalasia and 57 healthy controls were prospectively studied. CAA were assessed by indirect immunofluorescence on intestinal monkey tissue sections. Western blot on primate cerebellum protein extract and dot technique with highly purified recombinant neuronal antigens (Hu, Ri, and Yo) were further used to analyze target antigens of CAA. CAA were significantly increased in achalasia patients compared with controls when considering nuclear or cytoplasmic fluorescence patterns. (33% vs. 12%, P = 0.03 and 48% vs. 23%, P = 0.001 respectively). By immunoblot analysis, CAA did not target neuronal antigens, however 52/53 and 49 kDa bands were consistently detected. CAA positivity was not correlated to specific clinical features. The results are along with previous studies demonstrating high CAA prevalence in achalasia patients. When reviewing technical protocols and interpretation criteria, several discrepancies which could explain controversies between studies were noted.

Infectious agents as potential triggers for autoimmunity in achalasia

“…Recently, Kallel-Sellami et al, as well as our group, determined the levels of circulating antimyenteric antibodies in serum from patients with achalasia. The prevalence of nuclear, nucleolar, or cytoplasmic circulating antibodies against myenteric plexus in the sera from idiopathic achalasia patients was 63% and 100% versus 12% and 0% in the sera from healthy donors, respectively 12,72 .…”

“…The imbalance produced by loss of VIP and NO-secreting neurons can lead to irreversible esophageal motor dysfunction. Furthermore, the progressive destruction of myenteric ganglion cells and the occurrence of neural fibrosis would lead to achalasia 5,72 .…”

“…Most reports of pathological findings for human cases show the presence of neuronal autoantibodies 72,73 . These autoimmune constituents have been shown to directly contribute to the destruction of the myenteric plexus 74 .…”

“…Moreover, unusual staining patterns in the nuclei, such as cytoplasmic staining as in anti-Jo-1 (histidyl tRNA synthetase) positive polymyositis/dermatomyositis, and antimitochondrial antibodies have been determined 75 . At present, cytoplasmic structure has become highly relevant due to a critical role in the functions of siRNA and miRNAs 12,[72][73][74][75][76][77] .…”

“…Other studies also analyzed the target antigens of circulating antimyenteric autoantibodies. A majority (69-80%) of the sera samples from the idiopathic achalasia patients reacted against PNMA2 (Ma2/Ta; paraneoplastic antigen Ma2, Ma protein present in the nucleolus of the neurons), and GAD65; a few (8%) reacted with the recoverin antigen that is related to Sjögren's syndrome and none with Hu, CDR-62 (Yo), Nova-1 (Ri), SOX-1, titian, or amphiphysin, which could indicate that these proteins might be potential antigens present in the myenteric plexus that contribute to be one of the pathogenic mechanisms for the development of the disease 12,72,73,82 .…”