Histamine elevation in familial Mediterranean fever: A study from the Juvenile Inflammatory Rheumatism cohort

Nabiha Sbeih; Rim Bourguiba; Nadia Hoyeau-Idrissi; Jean-Marie Launay; Jacques Callebert; Danielle Canioni; Harry Sokol; Véronique Hentgen; Gilles Grateau; Olivier Hermine; Sophie Georgin-Lavialle

doi:10.1016/j.ejim.2023.06.009

Histamine elevation in familial Mediterranean fever: A study from the Juvenile Inflammatory Rheumatism cohort

Eur J Intern Med. 2023 Oct:116:89-95. doi: 10.1016/j.ejim.2023.06.009. Epub 2023 Jun 20.

Authors

Affiliations

¹ Department of Internal Medicine, National Reference Centre for Auto-inflammatory Diseases and inflammatory Amyloidosis (CEREMAIA), Tenon Hospital, AP-HP, Paris, France; Sorbonne Université, Inserm U938, Paris, France; Laboratory of Molecular mechanisms of Hematological disorders and therapeutic implications, INSERM U1163 and CNRS ERL 8254, Fondation Imagine, Paris, France.
² Department of Internal Medicine, National Reference Centre for Auto-inflammatory Diseases and inflammatory Amyloidosis (CEREMAIA), Tenon Hospital, AP-HP, Paris, France; Sorbonne Université, Inserm U938, Paris, France.
³ Service d'Anatomie Pathologique, Hôpital Saint-Antoine, AP-HP, Paris, France.
⁴ Service de Biochimie et Biologie Moléculaire, INSERM U942, Hôpital Lariboisière et Université Paris Cité, AP-HP, Paris, France.
⁵ Laboratoire d'Anatomie-Pathologie, Hôpital Necker-Enfants Malades, AP-HP et Université Paris Cité, Paris, France.
⁶ Service de Gastroentérologie et Nutrition, Hôpital Saint-Antoine, AP-HP, Paris, France et Sorbonne Université, Equipe AVENIR, Laboratoire INSERM U938, Paris, France; Equipe Interactions des bactéries commensales et probiotiques avec l'hôte, MICALIS, INRA, Jouy en Josas, France.
⁷ Department of General Pediatrics, André Mignot Hospital, National Reference Centre for Auto-inflammatory Diseases and inflammatory Amyloidosis (CEREMAIA), Versailles, France.
⁸ Department of Internal Medicine, National Reference Centre for Auto-inflammatory Diseases and inflammatory Amyloidosis (CEREMAIA), Tenon Hospital, AP-HP, Paris, France.
⁹ Centre de Référence des Mastocytoses, Service d'Hématologie adulte, Université Paris Cité, Hôpital Necker-Enfants malades, AP-HP, Paris, France; Laboratory of Molecular mechanisms of Hematological disorders and therapeutic implications, INSERM U1163 and CNRS ERL 8254, Fondation Imagine, Paris, France.
¹⁰ Department of Internal Medicine, National Reference Centre for Auto-inflammatory Diseases and inflammatory Amyloidosis (CEREMAIA), Tenon Hospital, AP-HP, Paris, France; Sorbonne Université, Inserm U938, Paris, France. Electronic address: [email protected].

PMID: 37349205
DOI: 10.1016/j.ejim.2023.06.009

Abstract

Background: Familial Mediterranean Fever (FMF) is the most frequent monogenic autoinflammatory disease (AID). Some patients have persistent symptoms despite colchicine intake. Mast cells (MC) are innate immune cells involved in inflammatory conditions including AID. Their activation is responsible for various symptoms such as abdominal pain, bloating and pruritus.

Objective: Our objective was to evaluate features of a systemic MC activation in FMF adult patients.

Methods: FMF adult patients prospectively filled a MC activation survey and usual MC mediators (tryptase and histamine in whole blood, plasma and urine) were measured. They were compared with a healthy control group (HC) and a systemic mastocytosis (SM) group. When digestive biopsies were realized during follow-up, MC infiltration in digestive mucosa was analyzed in FMF, in comparison with SM, Crohn disease (CD) and normal biopsies.

Results: Forty-four FMF patients, 44 HC and 44 SM patients were included. Thirty-one (70%) FMF patients had symptoms of mast cell activation, versus 14 (32%) in the HC group (p = 0.0006). Thirty (68%) FMF patients had at least one elevated MC mediator: mainly whole blood histamine, in 19 (43%) and urinary histamine, in 14 (32%), which were significantly higher than in HC subjects. MC infiltration was comparable in FMF digestive biopsies, biopsies of CD and normal biopsies but was lower than in SM biopsies.

Conclusion: FMF patients show frequent symptoms of MC activation and an increase of blood or urinary histamine never described before in this disease. This suggests an implication of MC and possibly basophils in FMF pathophysiology.

Keywords: Basophils; Familial Mediterranean fever; Histamine, Mast cells; Mast cell activation.

MeSH terms

Adult
Colchicine
Crohn Disease*
Familial Mediterranean Fever* / diagnosis
Histamine
Humans
Mast Cells
Mastocytosis, Systemic* / diagnosis
Rheumatic Fever*

Substances

Histamine
Colchicine