Glycosylated Ferritin in Macrophagic Activation Syndromes
Glycosylated Ferritin in Macrophagic Activation Syndromes
In healthy subjects, from 50 to 80 % of the serum ferritin is glycosylated [1, 2] . A
 decrease in the percentage of ferritin glycosylation can be observed in inflammatory
 diseases, malignancies, infections, or liver disease but is rarely less than 20% [3 , 4] .
 Percentage of glycosylated ferritin below 20% have been described in patients with adult
 Still's disease and haemophagocytosis lymphohistiocytic syndromes (HLH).

 The glycosylated ferritin has been included in the diagnostic criteria for Still's disease in
 adults. A cut-off of less than 20 % has a sensitivity and specificity of 72 and 69 %
 respectively , and 35 and 94 % when combined with a total ferritin level greater than 5 times
 normal value. This parameter was also suggested to be a more specific marker to confirm a
 diagnosis of HLH than a high ferritin level ( > 500μg / L). However, several limitations of
 this parameter were highlighted, some conditions making its interpretation difficult :
 particularly in cases of major hepatic cytolysis and severe sepsis (miliary tuberculosis,
 lymphoma and disease Adult Still).

 It is not always possible to distinguish severe sepsis, HLH syndrome and Still's disease.

 A fine analysis of various glycoforms components of ferritin could be used to distinguish
 different subgroups of patients. Few data are available on the mechanism of secretion and
 glycosylation of ferritin, but the investigators assume that the glycosylation patterns of
 ferritin may vary between different disease states and reflect distinct underlying
 pathophysiological mechanisms.
The objectives of this study are:

 1. . To evaluate the diagnostic performance of the assay of the glycosylated ferritin under
 HLH syndrome and Still's disease in adults.

 2. . To study the different glycoforms of ferritin from serum of patient with
 hyperferritinemia.

 Materials and methods

 1. Patient groups studied and control group

 -  Any suspicion of HLH or Still's disease syndrome in adults

 -  Control groups: sepsis, severe sepsis, septic shock, inflammation ( lupus,
 rheumatoid arthritis), severe hepatic necrosis, hematologic malignancy at diagnosis
 or relapse

 2 . Samples

 -  Serum will be collected for the determination of glycosylated ferritin in patients
 with suspicion of HLH syndrome or Still's disease in adults

 -  For the orther patients remaining serum samples will be collected from ferritin
 sample of the routine biological evaluation in patients with infammatory diseases (
 lupus, rheumatoid arthritis) , hematologic malignancies at diagnosis or relapse,
 hepatic necrosis or sepsis.

 3 . Characterization of patients based on diagnostic criteria (clinical and
 biological) retained (with collaborating physicians).

 After approval of the EC CHU Brugmann, the protocol will be submitted to other EC
 institutions.

 4 . Analysis of the glycosylation profile of ferritin by mass spectrometry. (in collaboration
 with the Faculty of Pharmacy , Department of Pharmaceutical Chemistry , Van Antwerpen P and
 Delporte C)

 Analysis and interpretation

 1. . Determination of the sensitivity and specificity of the diagnostic assay of the
 glycosylated ferritin under HLH syndrome and Still's disease .

 2. . Characterization of subgroups of patients according to the following information:
 Ferritin and its glycosylated fraction, documented infections , fever, MOF ,
 hepatomegaly, splenomegaly, haemophagocytosis (when bone marrow aspirate available),
 thrombocytosis, anemia, leukopenia, neutropenia, liver enzymes, hypertriglyceridemia,
 coagulopathy, hypofibrinogenemia, VS / CRP.

 3. . Analysis of glycosylation patterns according to the patient subgroup.
Inclusion Criteria:

 -  Suspicion of sepsis, macrophagic activation syndrome, Still's disease or
 hyperferritinemia (malignant disease, hepatic cytolysis)

 Exclusion Criteria:

 -  Normal ferritin level