IgA from HIV+ haemophilic patients triggers intracellular signals coupled to the cholinergic system of the intestine

Abstract

SUMMARYIgA was obtained from HIV-infected haemophilic patients and the intracellular signals triggered by its reaction with isolated rat intestinal strips were studied. HIV+IgA stained intestinal microvilli with a granular immunofluorescence pattern and bound to the muscarinic acetylcholine receptor (mAChR), displacing the specific muscarinic cholinergic antagonist QNB in a non-competitive manner. It triggered the signals that are the consequence of mAChR stimulation in the intestine. Thus, it decreased CAMP synthesis and increased guanosine 3':5'-cyclic monophosphate (cGMP) formation and phosphoinositide (PI) turnover of the intestine. In addition, it stimulated prostaglandin E2 (PGE2) synthesis by intestinal strips. Through its effect on PGE2 synthesis, HIVfIgA could have a dual action. On the one hand, it could enhance immunosuppression at a local level, favouring pathogen growth and subsequent intestinal dysfunction. On the other hand, PGE2 could directly increase intestinal motility and electrolyte/fluid loss. Both effects could be involved in intestinal damage in AIDS.

The impact of HIV/AIDS on compliance with antidepressant treatment in major depressive disorder: A prospective study in a South African private healthcare cohort

“…Our data infer that the reduced compliance with these antidepressants may have a biological basis, in particular an apparent increase in cholinergic sensitivity in the HIV/AIDS population. Indeed, cholinomimetic antibodies of the immunoglobulin (IgA) class are present in HIV/AIDS patients [ 58 , 59 ], suggesting that these patients may indeed be hypersensitive to drugs with activity on the cholinergic system [ 60 ]. Importantly, TCA and paroxetine non-compliance with TCAs and paroxetine can evoke a cholinergic overdrive [ 57 , 61 ], which may augment the hyper-cholinergic state present in HIV/AIDS patients, leading to a greater adverse experience and subsequent non-compliance.…”

Muscarinic receptors autoantibodies purified from mammary adenocarcinoma-bearing mice sera stimulate tumor progression

“…These Abs activate M 2 and M 3 muscarinic receptors intracellular signals respectively, promoting agonistic functions that impaired patients' conditions [16,17]. We had previously reported the presence of IgA Abs in the sera of haemophilic HIV+ patients that interact with ileal muscarinic receptors exerting parasympathetic actions on ileal motility by inducing IP3 and prostaglandin E 2 synthesis [18]. We observed that IgA-HIV+ was a more potent stimulus than CARB to activate ileal cholinoceptors in the same manner than ETB IgG, that stimulates LM3 cells' proliferation 3-fold more than CARB.…”