Transfusion related immunomodulation

( TRIM )
TRIM
• TRIM can be defined as the constellation of the laboratory
immune aberrations that occur after allogeneic blood
transfusion(ABT) and their established or purported clinical
effects.

• Includes both immunomodulatory and proinflammatory effects

of transfusion.
TRIM
• Transfusion of allogeneic blood can result in either
alloimmunization or immune tolerance.

• The presence or absence of autologous HLA DR antigens

on the donor WBCs determines the response.

• Fully mismatched HLA DR antigens- Alloimmunization

• At least one HLA DR antigen shared- Tolerance
• The transfusion of allogeneic blood products results in the
recipients being exposed to large amounts of foreign antigens
(alloantigens) in both the soluble and the cell-associated form.

• The presence of these alloantigens in the circulation can create

conditions for a variety of possible immunological responses,
which include both alloimmunization and the downregulation of
immune responses.

• The latter effect generally has been referred to transfusion-

associated immunomodulation, or TRIM.
 Changes in recipient’s lymphocytes after
blood transfusion

• Atypical lymphocytes increase by a factor of five or more.

• Decrease in NK function and delayed hypersensitivity

• These changes are interpreted as a response to donor HLA antigens.

 Proposed mechanisms of TRIM:

• At first glance, the combination of :

• alloimmunization (which is a positive immune response)
• and other TRIM effects (which are generally immunosuppressive) may seem
contradictory.
• leukocytes in transfused RBCs may simultaneously enhance
humoral immunity whilst suppressing cellular immunity. In
this way, enhanced antibody responses and cellular
immunosuppression may simultaneously occur (decreased
helper to suppressor T-lymphocyte ratio; decreased NK cell
function; defective antigen presentation; and reduction in cell
mediated immunity).
Accepted TRIM effects:
• Solid organ transplantation:
• Since the 1960s, transfusion of whole blood prior to organ
transplantation results in significantly improved allograft survival in
both humans and experimental animals.
• This effect was most notable for transplanted cadaveric kidneys.
• “Transfusion effect,” occurs to the greatest extent with the
transfusion of :
• whole blood,
• to a lesser extent with packed RBCs,
• and to an even smaller extent with washed or frozen/thawed RBC products, which are
> 80–90% leukocyte reduced.
• There is little or no effect when giving stringently leukodepleted
products (99.9% leukoreduced).
• This generally has not seen widespread use due to
concern that allogeneic blood products might be
associated with the transmission of viral infections
(i.e. HIV, HCV etc.)
• Reduction in the likelihood of spontaneous
abortion:

• It has been observed that transfusion of allogeneic

blood, from paternal or other sources, has a
beneficial effect in preventing recurrent
spontaneous abortion, possibly by decreasing the
T-cell response and generating suppressor T cells.

• Although the effect is mild, .

Debated TRIM effects:
• Cancer, infection and autoimmunity:
• TRIM effects have been reported in situations in
which mild impairment of cellular immunity may be
predicted to result in alterations in pathology.

• For example, published data suggest that

transfusion may increase cancer recurrence and/or
metastasis, presumably due to decreased
antitumor immunity.
• Likewise, published data demonstrate that
increased post-operative infections correlate with
transfusion, suggesting TRIM inhibition of anti-
microbial immunity.
• Also, studies suggest that transfusion may have a
therapeutic benefit in certain autoimmune states
(such as Crohn’s disease).
• It is reasonable to conclude that clinically
significant TRIM effects in cancer, post-operative
wound infections and autoimmune disorders may
or may not occur, and thus remain disputed.
 Clinical effects of TRIM

Beneficial Effects: Deleterious Effects:

• Enhanced Survival of Renal • Increased Recurrence of Resected
Allografts Malignancies

• Reduced Risk of Recurrent • Increased Risk of Postoperative Bacterial

Spontaneous Abortions Infection

• Reduced Risk of Recurrence of • Increased Risk of Short-Term Mortality

Crohn’s Disease
 These effects may be mediated by
1)Soluble HLA Class I peptides that circulate in allogeneic
plasma;

2) Soluble biologic response modifi ers released in a time-

dependent manner from WBC granules or membranes into
the supernatant fluid of Red Blood Cell (RBC) or platelet
concentrates during storage;

3) Allogeneic mononuclear cells

Thank you