Does Antithymocyte Globulin (ATG) affect procalcitonin levels in transplant recipients?

ATG Significantly Elevates Procalcitonin Levels Without Infection

Yes, antithymocyte globulin (ATG) causes marked, clinically significant elevations in procalcitonin levels in transplant recipients, reaching levels comparable to severe sepsis (up to 600 ng/ml) despite the complete absence of infection. 1, 2

Mechanism and Time Course

ATG triggers a massive surge in procalcitonin through direct effects on T lymphocytes, with the following predictable pattern:

• Peak elevation occurs 1 day after ATG administration, with procalcitonin levels rising from normal baseline to levels that would otherwise indicate severe bacterial infection 1
• TNF-alpha elevation precedes the procalcitonin rise, suggesting cytokine-mediated induction rather than infectious etiology 2
• Levels return to baseline by day 3-4 after the initial dose, regardless of continued ATG administration 1
• This pattern occurs with both rabbit ATG (thymoglobulin) and equine ATG, but notably does NOT occur with anti-IL-2 receptor antibodies or steroid bolus therapy alone 2

Critical Clinical Implications

Procalcitonin cannot be used as a marker of infection during or immediately after ATG therapy. The following considerations are essential:

• Procalcitonin elevations during ATG treatment are independent of actual infection status and occur even in patients with negative microbiological cultures 1
• The magnitude of procalcitonin elevation (up to 600 ng/ml) overlaps completely with levels seen in severe sepsis, making differentiation impossible based on the number alone 2
• C-reactive protein follows a similar pattern of non-infectious elevation during ATG therapy, rendering it equally unreliable 1
• Procalcitonin levels are independent of renal and liver function, so organ dysfunction does not explain the elevation 1

Monitoring Strategy During ATG Therapy

Given the unreliability of procalcitonin during ATG administration, use this approach:

• Do not rely on procalcitonin or CRP for infection diagnosis during the first 5 days of ATG therapy 1, 2
• Clinical assessment, microbiological cultures, and radiologic findings must guide infection diagnosis during this period 3
• If infection is suspected after day 7-11 post-ATG, procalcitonin may regain utility, though the dynamics differ from non-ATG patients 1
• White blood cell count decreases predictably after ATG (due to T-cell depletion), further limiting traditional infection markers 1

Infectious Risk Context

While procalcitonin is unreliable during ATG therapy, the actual infection risk remains substantial:

• Infectious complications occur in approximately 39% of patients receiving ATG for rejection treatment 4
• Common infections include bacterial (37%), fungal (18%), and viral (10%) pathogens, with pulmonary aspergillosis and CMV being particularly concerning 5, 4
• Prophylactic antimicrobial therapy is essential during and after ATG treatment 5
• Monitor with daily CBC and hepatic/renal function tests during ATG initiation, along with regular cultures 6

Practical Algorithm

When evaluating potential infection in ATG-treated transplant recipients:

1. Days 0-5 of ATG: Expect procalcitonin elevation regardless of infection; rely on clinical signs, cultures, and imaging 1, 2
2. Days 6-10 post-ATG: Procalcitonin may still be unreliable; continue culture-based diagnosis 1
3. Beyond day 10: Procalcitonin may regain diagnostic value, but interpret cautiously in context of clinical picture 1
4. Any timepoint: Never use procalcitonin as the sole criterion for starting or stopping antibiotics in ATG recipients 3, 1