D3.420 - IL-1β, IL-6, and TNF serum levels in mastocytosis are not correlated with psychometric measures, though they correlate to serum tryptase and recurrent edemas

Mastocytosis is a rare neoplastic disorder of the bone marrow, characterized by the uncontrolled proliferation and accumulation of mast cells in various tissues. It manifests through a range of symptoms, including those related to mast cell degranulation such as urticaria, edema, diarrhea, bronchospasm, anaphylaxis, and headaches, as well as symptoms from pathological mast cell infiltration. While the physical symptoms of mastocytosis are well-known, neuropsychiatric disorders are common among patients. However, the underlying mechanisms behind these symptoms remain poorly understood. Recent research suggests that pro-inflammatory cytokines such as IL-1β, IL-6, and TNF may contribute to impairment in psychometric measures such as cognitive impairment in systemic mastocytosis. We aimed to study the role of pro-inflammatory cytokines in psychometric measures and other mast cell degranulation symptoms in patients with mastocytosis.

Patients with systemic mastocytosis who provided informed consent at the Department of Allergology in Gdańsk were enrolled to this observational registry. Psychometric measures were performed: the Mini Mental State Examination (MMSE), the Quality of Life in Mastocytosis questionnaire, the Hamilton 17-item Depression Scale, the Pruritus Visual Analog Scale. In addition, we evaluated serum tryptase concentration, archival bone marrow biopsy results, and IL-1β, IL-6, and TNF concentrations. The relation of those variables to other mast cell degranulation symptoms was evaluated in secondary analysis.

Among 115 patients, the primary outcomes showed no significant correlation between IL-1β, IL-6, or TNF levels and cognitive dysfunction or depression severity. The secondary outcomes revealed strong relations between IL-1β and IL-6 concentrations (p= 0.000 CI: 2.08493    2.638383). Serum tryptase related to TNF (p= 0.002 CI:.0119092 .0527313), IL-1β (p=0.000 CI: .0195095 .0494227), and IL-6 (p=0.000 CI:.0460549 .1160085). Additionally, IL-6 (p =0.001 CI: 3.049534–11.05441) and IL-1β (p =0.000 CI: 0.9842632–4.512159) levels were significantly related to edema.

While no correlation was found between serum cytokine levels and psychometric measures, significant associations between tryptase and pro-inflammatory cytokines suggest a link between mast cell activation and systemic inflammation. This highlights the importance of further research into cytokine-targeted therapies particularly in patients with recurrent edemas as leading symptom.