SOLUBLE TREM-1

LEVELS IN
FAMILIAL Prof. Dr. Serdal Ugurlu
Bugra Han Egeli
MEDITERRANEAN bugraegeli@gmail.com

FEVER RELATED AA- Istanbul University-

Cerrahpasa
AMYLOIDOSIS
 Autoinflammatory diseases manifest themselves
with recurrent episodes of fever, and end organ
damage. Monocytes and neutrophils are key to this
inflammatory condition. The most common of these
diseases being Familial Mediterranean Fever (FMF)
is clinically defined as recurrent self-limiting
attacks of fever and inflammation of the serosa.

https://i0.wp.com/www.pathologystudent.com/wp-content/uploads/2009/04/leukocytes.jpg?resize=500%2C332&ssl=1
WHAT IS
TREM-1?
 Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) is a member of a
family of cell surface receptors of innate and adaptive immunity.

 Cytokine production, neutrophil degranulation, and phagocytosis.

 IL‐1β, IL‐2, IL‐6, IL‐8, IL‐12p40, and TNF‐α.

 The major role of IL-1 β in the pathogenesis of autoinflammatory diseases

should be highlighted here as its inhibition even has an impact on current
treatment methods. In addition to cytokines, the up-regulation of reactive
oxygen species, lactoferrin, and myeloperoxidase following TREM-1
stimulation also amplifies the inflammation via further neutrophil degranulation.

 Molecular cross-linking between TREM-1 cascade and the intracellular cascades

of Toll-like Receptor 2 and 4 (TLR 2, 4) is prominent in amplifying the
inflammatory response.

https://www.qiagen.com/geneglobe/static/images/Pathways/TREM1%20Pathway.jpg
SOLUBLE TREM-1
Another important concept is soluble form
of TREM-1 (sTREM-1). It is a 27kDA
glycosylated peptide, and a cleaved product
of the extracellular part of the receptor.
Plasma, bronchoalveolar lavage, synovial
fluid, and cerebrospinal fluid
Septic shock, viral infections such as
influenza, filoviruses, flaviviruses, alpha
viruses, pneumonia, bacterial meningitis,
malignancies, inflammatory bowel disease

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RHEUMATOLOG
Y
 Scleroderma

 Behcet's disease

 Rheumatoid arthritis

 Systemic lupus erythematosus

 Inflammatory bowel disease

 No FMF

https://www.unmc.edu/intmed/divisions/rheum/index.html
THE AIM OF THIS STUDY

Clinical role of
sTREM-1 in Predictive marker
management and of amyloidosis
follow-up of FMF
METHODS
 Participants
 Cohort of the study includes 62 patients with
FMF (42 with amyloidosis)
 For control purposes 5 patients with AA
amyloidosis secondary to other
inflammatory diseases (2 juvenile idiopathic
arthritis (JIA), 1 RA, 1 Ankylosing
Spondylitis (AS), 1 idiopathic amyloidosis)
 20 healthy individuals were also included
METHODS
 Venous blood samples
 Enzyme linked immunoassay (ELISA)
method
 Serum CRP and creatinine levels were
measured by immunoturbidimetric and
photometric methods, respectively.

http://www.biobest.co.uk/assets/images/home/blood-samples-web.jpg
 FMF (+) A * (+) (n=42) FMF (+) A * (-) (n=20) FMF (+) * (n=62) FMF (-) A (+) * (n=5) HC * (n=20)
Female, n (%) 19 (45.24) 9 (45) 28 (45.16) 1 (20) 10 (50)
Mean Age (yrs, mean ±SD) 43.93±12.89 35.3±9.64 41.15±12.54 54.8±18.97 35.4±6.57
Mean Age of FMF Dx (yrs, mean ±SD) 15.15±11.83 14.84±9.69 15.05±11.01 N/A N/A
Mean Duration of FMF Disease (yrs, mean ±SD) 27.76±12.57 19.74±11.88 25.22±12.82 N/A N/A
Presenting Symptoms, n (%)
  Abdominal Pain 35 (83.33) 18 (90) 53 (85.48) N/A N/A
  Chest Pain 22 (52.38) 11 (55) 33 (53.23) N/A N/A
  Fever 35 (83.33) 18 (90) 53 (85.48) N/A N/A
  Arthralgia 38 (90.48) 16 (80) 54 (87.1) N/A N/A
  Arthritis 30 (71.43) 13 (65) 43 (69.35) N/A N/A
  No Symptoms 1 (2.38) 0 (0) 1 (1.61) N/A N/A

RESULTS
Treatment, n (%)
  Colchicine 41 (97.62) 19 (95) 60 (96.77) N/A N/A
  Anakinra 29 (69.05) 1 (5) 30 (48.39) N/A N/A
  Canakinumab 9 (21.43) 3 (15) 12 (19.35) N/A N/A
  Tocilizumab 6 (14.29) 0 (0) 6 (9.68) N/A N/A
MEFV gene status, n (%)
  M694V Homozygous 28 (67.67) 11 (55) 39 (62.9) N/A N/A
  M694V Heterozygous 9 (21.43) 8 (40) 17 (27.42) N/A N/A
  M694V+Exon 10 (M680I, V726A, M694I) Compound Heterozygous 2 (4.76) 0 (0) 2 (3.23) N/A N/A
  Other 9 (21.43) 0 (0) 9 (14.52) N/A N/A
  Negative MEFV gene mutation 1 (2.38) 0 (0) 1 (1.61) N/A N/A
  Unknown 2 (4.76) 0 (0) 2 (3.23) N/A N/A

RESULTS
 Cr <1.5 (n=32) Cr>1.5 (n=15) p

Age 43.03±13.58 49.47±13.71 0.138

TREM-1 487.03±218.79 1435.47±883.96 <0.0001

CRP 11±15.35 12.93±18.33 0.71

Creatinine 0.93±0.27 3.68±2.46 <0.0001

RESULTS
RESUL
TS
 The results of this study showed that sTREM-1 sTREM-1 levels were not found elevated in FMF
levels were elevated in amyloidosis patients when patients when compared to healthy controls.
compared to FMF patients and healthy controls.

DISCUSSION
DISCUSSION

sTREM-1 levels were significantly higher

in FMF related Amyloidosis patients, Soluble TREM-1 seems to be related to
when the statistical analysis included only renal function rather than disease activity
the patients with preserved renal function in amyloidosis.
this difference was absent.

The association of elevated sTREM-1

levels and kidney injury is already present
Soluble TREM-1 is inadequately studied
in literature. The kidney injury caused by
among human participants in kidney
amyloid deposition can result in an
injury
inflammatory response explaining
elevated sTREM-1 levels.
TAKE HOME MESSAGES
It is not possible to say that sTREM-1 is superior to non-specific acute phase reactants in FMF
especially when patients are not in attack period.

sTREM-1 seems to be related to renal function rather than disease activity in amyloidosis. Its
association with acute renal injury has already been reported in a study with human
participants.

Its role as an early diagnostic marker of amyloidosis in FMF as well as in other pathologies
complicated with AA amyloidosis should be tested in larger patient groups bearing in mind the
kidney injury.