ABSTRACT
OBJECTIVE: The aim of our study was to analyze the clinical and functional effect of the p.Q703K (p. Q705K, c. 2107C>A) variant of the NLRP3 gene in a population of patients screened for suspected cryopyrin-associated periodic syndrome (CAPS). METHODS: Since 2002, 580 patients underwent molecular analysis for NLRP3. Data on clinical presentation, response to treatment, and longterm followup were collected using a uniform questionnaire. The pattern of cytokine secretion after lipopolysaccharide stimulation from isolated monocytes was analyzed in 3 patients carrying the p.Q703K variant and 1 patient with a chronic infantile neurologic, cutaneous, articular syndrome phenotype carrying both the p.M406I and p.Q703K, and compared with 7 patients with CAPS with sure pathogenic variants and 6 healthy controls. RESULTS: The p.Q703K variant was found in 57 screened patients with an overall allelic frequency of 5%. The frequency in normal controls was 5.5%. Clinical data at the moment of molecular analysis and at followup were available in 36 patients. Two patients displayed additional mutations of NLRP3. The mean followup was 2.5 years. Thirteen patients (39%) had a final diagnosis different from the original suspicion of CAPS. The remaining 21 patients displayed a mild phenotype mainly characterized by recurrent episodes of urticarial rash and arthralgia. Only 8 patients were treated with anti-interleukin (IL)-1 treatment, with a complete response in 5 patients. The pattern of secretion of IL-1ß and other cytokines (IL-6 and IL-1 receptor antagonist) in patients did not display the aberrancies observed in patients with CAPS and was similar to that observed in healthy controls. CONCLUSION: The present study confirms the weak clinical and functional effect of the p.Q703K variant.
Subject(s)
Arthralgia/etiology , Cryopyrin-Associated Periodic Syndromes/diagnosis , Exanthema/etiology , Mutation , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Phenotype , Adolescent , Adult , Arthralgia/genetics , Arthralgia/metabolism , Child , Child, Preschool , Cryopyrin-Associated Periodic Syndromes/complications , Cryopyrin-Associated Periodic Syndromes/genetics , Cytokines/metabolism , Exanthema/genetics , Exanthema/metabolism , Female , Humans , Infant , Male , Middle Aged , Monocytes/metabolism , Young AdultABSTRACT
Echinococcosis/hydatidosis is a parasitic zoonosis caused in humans by the larval stage of the Echinococcus granulosus cestode. Although notification of infestation is required, there are no reliable data on the prevalence of this parasitosis among humans in Italy. This zoonosis was first reported in ancient times (Hippocrates, fourth century BC) and since then many cases of echinococcosis/hydatidosis have been described. Currently, it is considered one of the main parasitoses affecting animals bred for income and one of the most important parasitic zoonoses. We present the clinical case of a three-year-old child, living in Palermo with a dog in his house, who came to our observation for dyspnea occurring after physical exercise. Diagnosis of echinococcosis was performed on the operating table and by histological examination. The case presented is special in its manifestation from a clinical point of view, because the young patient experienced multiple injuries only to lungs, without involvement of other organs and, although the left lung cysts appeared fissured on the operating table, our patient never presented immunoallergic disorders.
