Ferritinemia and serum inflammatory cytokines in Swedish adults with Gaucher disease type 1.
The storage of glucosylceramide in macrophages produces an inflammatory response in Gaucher disease type 1 (GD1) resulting in iron metabolism dysregulation and cytokine release.



The study included 16 adults with GD1 aged 20-86years. All but one patient carried at least one allele with the c.1226A>G (N370S) mutation in the GBA1 gene. Ferritinemia, iron metabolism profiles including hepcidin, and inflammatory cytokine concentrations were assessed in GD1 patients in Sweden.



Hyperferritinemia was present in 81% of patients. There was no correlation between hyperferritinemia and patient's gender, spleen status, or clinical status. Hepcidin was discrepantly low in relation to ferritin levels. TNF-α was moderately increased in 5 of 11 patients; 2 patients with the highest TNF-α concentrations showed mildly elevated IL-6 levels. The concentrations of IL-1β, IL-8, and IL-10 were normal in all patients. Upon treatment, ferritinemia ameliorated but S-ferritin levels did not normalize. The increased TNF-α level however, normalized in all treated patients, reaching the lowest values after 2years of therapy and continued to be stable during the remaining 2years of follow-up.



Hyperferritinemia is a frequent finding in GD1 in Sweden. The relatively low hepcidin levels reveal a distorted relationship between hepcidin and ferritin in GD1. Therapy has the potential to not only ameliorate hyperferritinemia but to also normalize the serum TNF-α concentration in GD1.
Department of Radiation Sciences, Section of Hematology, Umeå University, Umeå, Sweden.
Fryderyk
F
Lorenz
Hematology Center Karolinska, Department of Medicine at Huddinge, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Ewa
E
Pawłowicz
Department of Clinical Pathology and Cytology, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Monika
M
Klimkowska
Department of Clinical Chemistry, Unilabs and Institution for Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
Soheir
S
Beshara
Hematology Center Karolinska, Department of Medicine at Huddinge, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Agnes
A
Bulanda Brustad
Department of Hematology, Jagiellonian University Medical College, Krakow, Poland.
Aleksander B
AB
Skotnicki
Department of Radiation Sciences, Section of Hematology, Umeå University, Umeå, Sweden.
Anders
A
Wahlin
Hematology Center Karolinska, Department of Medicine at Huddinge, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden; Medical Faculty, University of Rzeszow, Rzeszow, Poland. Electronic address: maciej.machaczka@ki.se.
Maciej
M
Machaczka
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016207:Cytokines / Q000097:blood*; D005260:Female; D005293:Ferritins / Q000097:blood*; D005776:Gaucher Disease / Q000097:blood* / Q000150:complications* / Q000453:epidemiology; D064451:Hepcidins / Q000097:blood; D006801:Humans; D019190:Iron Overload / Q000097:blood* / Q000150:complications* / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D013548:Sweden / Q000453:epidemiology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D055815:Young Adult
D016207:Cytokines; D064451:Hepcidins; D014409:Tumor Necrosis Factor-alpha; D005293:Ferritins
Cytokines; Enzyme replacement therapy; Gaucher disease; Hyperferritinemia; Substrate reduction therapy; TNF-α