STEPTRACKERIMMUNOLOGY + NEPHROLOGY | TRANSPLANT | HIGH-YIELD REVIEW

Transplant Rejection & GVHD

Rejection is sorted by timing, and timing reflects mechanism — preformed antibody in minutes, T cells in weeks, slow vascular and fibrotic injury over years. In GVHD the graft attacks the host.

FOCUS ON
Hyperacute (minutes): preformed anti-ABO or anti-HLA antibodies → complement, thrombosis, gray cyanotic graft → remove; prevented by crossmatch. Acute (weeks–months): cellular — CD8⁺ T cells against donor MHC (lymphocytic infiltrate, tubulitis, endotheliitis; reversible with steroids, antithymocyte globulin); antibody-mediated — new donor-specific antibodies, C4d in capillaries → plasmapheresis, IVIG, rituximab. Chronic (months–years): CD4⁺ T cells + antibodies → vascular smooth muscle proliferation and fibrosis (graft arteriosclerosis; bronchiolitis obliterans in lung; coronary vasculopathy in heart; vanishing bile ducts in liver) — irreversible. GVHD: donor T cells in an immunocompromised host (marrow, liver, unirradiated blood) attack skin, liver, gut (rash on palms/soles, jaundice, diarrhea); graft-versus-tumor is the benefit.
TYPE
TIMING · MECHANISM
PATHOLOGY
MANAGEMENT
Hyperacute rejection
Minutes · preformed anti-ABO/anti-HLA antibodies (type II)
Complement activation, thrombosis, ischemic necrosis; graft turns mottled and cyanotic on the table
Remove graft · prevent with ABO match + crossmatch
Acute cellular rejection
Weeks–months · CD8⁺ (and CD4⁺) T cells vs donor MHC (type IV)
Interstitial lymphocytes, tubulitis, endotheliitis (vasculitis)
Pulse steroids, antithymocyte globulin · reversible
Acute antibody-mediated rejection
Weeks–months · new donor-specific antibodies
Capillaritis, neutrophils, C4d deposition
Plasmapheresis, IVIG, rituximab
Chronic rejection
Months–years · T cells + antibodies + cytokines
Concentric intimal thickening (graft arteriosclerosis), interstitial fibrosis, tubular atrophy
Irreversible · major cause of late graft loss
Organ-specific chronic rejection
—
Kidney: fibrosis, ↑ creatinine · Lung: bronchiolitis obliterans · Heart: accelerated coronary vasculopathy · Liver: vanishing bile duct syndrome
—
Acute GVHD
Days–100 days · donor T cells vs host HLA
Maculopapular rash (palms, soles, ears), cholestatic hepatitis, profuse diarrhea
Steroids · risk ↑ with HLA mismatch
Chronic GVHD
> 100 days
Scleroderma-like skin, sicca, oral lichenoid lesions, bronchiolitis obliterans
Immunosuppression · ruxolitinib
Graft-versus-tumor effect
Donor T cells kill residual leukemia
Benefit of allogeneic marrow transplant
Donor lymphocyte infusion
Graft types
Autograft (self) · isograft (identical twin) · allograft (same species) · xenograft (other species)
Rejection risk rises from left to right
Autograft: no rejection
HLA matching
HLA-A, -B, -DR (DR most important for kidney)
Siblings: 25% full match
Panel reactive antibodies predict sensitization (prior transplant, pregnancy, transfusion)
Post-transplant infections · cancers
< 1 month nosocomial · 1–6 months CMV, PCP, BK · > 6 months community
PTLD (EBV), skin squamous cell carcinoma, Kaposi
Valganciclovir, TMP-SMX prophylaxis

Mechanism — two ways T cells see a graft

Direct allorecognitionRecipient T cells see intact donor MHC on donor APCs
→
Acute cellular rejectionStrong, early
Indirect allorecognitionRecipient APCs present donor peptides on self-MHC
→
Chronic rejection, antibody help

Rejection at a glance

TYPE
ONSET
EFFECTOR
REVERSIBLE?
Hyperacute
Minutes
Preformed antibody
No
Acute
Weeks–months
T cells ± new antibody
Yes
Chronic
Months–years
T cells + antibody, fibrosis
No
GVHD
Days–months
Donor T cells
Often

How it's tested

COMMON CONFUSIONRising creatinine after kidney transplant: acute rejection vs calcineurin-inhibitor nephrotoxicity vs BK nephropathy vs obstruction — biopsy distinguishes.
THE TRAPGVHD needs immunocompetent donor cells in a host that can't reject them — liver and marrow transplants and unirradiated blood in immunodeficient patients.
YOUR APPROACHTime since transplant → mechanism (preformed antibody, T cells, chronic) → biopsy finding → reversible or not → treatment.

If you see… think…

Kidney turns gray and mottled minutes after reperfusion → hyperacute rejection
Test preventing hyperacute rejection → crossmatch
Tubulitis with lymphocytes 6 weeks after transplant → acute cellular rejection
C4d in peritubular capillaries → antibody-mediated rejection
Concentric arterial intimal thickening years later → chronic rejection
Progressive dyspnea with obstruction after lung transplant → bronchiolitis obliterans
Rash on palms, jaundice and diarrhea after marrow transplant → acute GVHD
Benefit of donor T cells against leukemia → graft-versus-tumor
Most important HLA locus to match for kidney → HLA-DR
EBV-driven lymphoma after transplant → PTLD