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. 2023 Nov 29;24(23):16922.
doi: 10.3390/ijms242316922.

The Haptoglobin Response after Aneurysmal Subarachnoid Haemorrhage

Soham Bandyopadhyay  1   2 , Patrick Garland  1 , Ben Gaastra  1   2 , Ardalan Zolnourian  2 , Diederik Bulters  1   2 , Ian Galea  1   2
Affiliations

The Haptoglobin Response after Aneurysmal Subarachnoid Haemorrhage

Soham Bandyopadhyay et al. Int J Mol Sci. .

Abstract

Haptoglobin is the body's first line of defence against the toxicity of extracellular haemoglobin released following a subarachnoid haemorrhage (SAH). We investigated the haptoglobin response after SAH in cerebrospinal fluid (CSF) and serum. Paired CSF and serum samples from 19 controls and 92 SAH patients were assayed as follows: ultra-performance liquid chromatography for CSF haemoglobin and haptoglobin, immunoassay for serum haptoglobin and multiplexed CSF cytokines, and colorimetry for albumin. There was marked CSF haptoglobin deficiency: 99% of extracellular haemoglobin was unbound. The quotients for both CSF/serum albumin (qAlb) and haptoglobin (qHp) were used to compute the CSF haptoglobin index (qHp/qAlb). CSF from SAH patients had a significantly lower haptoglobin index compared to controls, especially in Haptoglobin-1 allele carriers. Serum haptoglobin levels increased after SAH and were correlated with CSF cytokine levels. Haptoglobin variables were not associated with long-term clinical outcomes post-SAH. We conclude that: (1) intrathecal haptoglobin consumption occurs after SAH, more so in haptoglobin-1 allele carriers; (2) serum haptoglobin is upregulated after SAH, in keeping with the liver acute phase response to central inflammation; (3) haptoglobin in the CSF is so low that any variation is too small for this to affect long-term outcomes, emphasising the potential for therapeutic haptoglobin supplementation.

Keywords: cerebrospinal fluid; cytokines; haemoglobin; haptoglobin; subarachnoid haemorrhage.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The levels of cerebrospinal fluid (CSF) haptoglobin (Hp) by Hp phenotype in subarachnoid haemorrhage (SAH) patients and controls. * p < 0.05; ns = not significant.
Figure 2
Figure 2
Factors influencing cerebrospinal fluid (CSF) haptoglobin concentration in the healthy state (A) and after SAH (B). CSF haptoglobin would increase as a result of higher serum haptoglobin and increased blood–brain barrier permeability, as well as upregulation of intrathecal haptoglobin synthesis. CSF haptoglobin would decrease as a result of intrathecal CD163-mediated uptake of haemoglobin–haptoglobin complexes after SAH. The intrathecal haptoglobin index corrects for serum haptoglobin levels and blood–brain barrier permeability, so that it becomes a measure of the balance between intrathecal synthesis and CD163-mediated consumption of haptoglobin. CSF = cerebrospinal fluid. BBB = blood–brain barrier.
Figure 3
Figure 3
(A) Haptoglobin (Hp) index by Hp phenotype in subarachnoid haemorrhage (SAH) patients and controls. (B) Difference in Hp index between controls and patients (positive values represent a higher Hp index in controls). * p < 0.05; ns = not significant.
Figure 4
Figure 4
The levels of serum haptoglobin (Hp) by Hp phenotype in subarachnoid haemorrhage (SAH) patients and controls. * p < 0.05; ns = not significant.
Figure 5
Figure 5
The liver acute phase response to central inflammation.
Figure 6
Figure 6
Scree plot of the principal components for cerebrospinal fluid cytokines. The horizontal dotted line represents an eigenvalue of 1.
Figure 7
Figure 7
Patient flow diagram of participant inclusion and exclusion.
See this image and copyright information in PMC

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