Gc-globulin is an acute phase reactant and an indicator of muscle injury after spinal surgery

Dahl, Benny; Schiødt, Frank Vinholt; Gehrchen, Martin; Ramlau, J.; Kiaer, T; Ott, Peter

doi:10.1007/s000110050722

Cited by 31 publications

(28 citation statements)

References 37 publications

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“…The ratio of bioavailable to total 25(OH)D in our cohort was 10-50%, largely tracking with VDBP haplotype (see Figure 4). This is a higher range than reported in the adult ICU population, which was 15% overall (15), or in healthy adults, in whom the ratio of bioavailable to total 25(OH)D also varied by race from 12 to 18% (33 VDBP has a myriad of effects, including actin scavenging during times of injury (44)(45)(46), production of the antimicrobial peptide cathelicidin (48), macrophage activation (especially in the lung), and urinary excretion of 25(OH)D (60), that could influence the severity and outcome of critical illness. GC2 carriers have an increased risk of tuberculosis infection (61) but a decreased risk of chronic obstructive pulmonary disease (62,63).…”

Section: Original Researchmentioning

confidence: 76%

“…VDBP plays a role in the immune system, the lung, and scavenging actin. VDBP levels have been shown to be decreased in times of diffuse inflammation, including in sepsis, severe trauma, and after surgery (44)(45)(46). In addition, certain disease states, including diffuse inflammation and critical illness, have been shown to be associated with lower VDBP levels (44,46).…”

Section: Low Serum Concentrations Of Total 25-hydroxyvitamin D (25[oh]d)mentioning

confidence: 99%

“…VDBP levels have been shown to be decreased in times of diffuse inflammation, including in sepsis, severe trauma, and after surgery (44)(45)(46). In addition, certain disease states, including diffuse inflammation and critical illness, have been shown to be associated with lower VDBP levels (44,46). VDBP concentration and haplotype influence the proportion of bioavailable vitamin D (32)(33)(34)47), meaning that the biologic activity of vitamin D could be similar in patients with widely different total 25(OH)D levels.…”

Section: Low Serum Concentrations Of Total 25-hydroxyvitamin D (25[oh]d)mentioning

confidence: 99%

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Critically Ill Children Have Low Vitamin D Binding Protein, Influencing Bioavailability of Vitamin D

Madden¹,

Feldman²,

Chun³

et al. 2015

Annals ATS

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Rationale: Vitamin D deficiency, often defined by total serum 25-hydroxyvitamin D (25[OH]D) ,20 ng/ml, is common in critically ill patients, with associations with increased mortality and morbidity in the intensive care unit. Correction of vitamin D deficiency in critical illness has been recommended, and ongoing clinical trials are investigating the effect of repletion on patient outcome. The biologically active amount of 25(OH)D depends on the concentration and protein isoform of vitamin D-binding protein (VDBP), which is also an acutephase reactant affected by inflammation and injury.Objectives: We performed a secondary analysis of a cohort of critically ill children in which we reported a high rate of vitamin D deficiency, to examine how VDBP level and genotype would impact vitamin D status. Methods:We prospectively enrolled 511 children admitted to the pediatric intensive care unit over a 12-month period. Measurements and Main Results:We measured serum VDBP in 479 children. We genotyped single nucleotide polymorphisms rs7041 and rs4588 in the VDBP gene (GC) to determine haplotypes GC1F, GC1S, and GC2 in 178 subjects who consented, then calculated bioavailable 25(OH)D from serum 25(OH)D, VDBP, albumin, and GC haplotype. The median serum VDBP level was 159 mg/ml (interquartile range, 108-221), lower than has been reported in healthy children. Factors predicting lower levels in multivariate analysis included age ,1 year, nonwhite race, being previously healthy, 25(OH)D ,20 ng/ml and greater illness severity. In the subgroup that was genotyped, GC haplotype had the strongest association with VDBP level; carriage of one additional copy of GC1S was associated with a 37.5% higher level (95% confidence interval, 31.9-44.8; P , 0.001). Bioavailable 25(OH)D was also inversely associated with illness severity (r = 20.24, P , 0.001), and ratio to measured total 25(OH)D was variable and related to haplotype.Conclusions: Physiologic deficiency of 25(OH)D in critical illness may be more difficult to diagnose, given that lower VDBP levels increase bioavailability. Treatment studies conducted on the basis of total 25(OH)D level, without consideration of VDBP concentration and genotype, may increase the risk of falsely negative results.

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Section: Original Researchmentioning

confidence: 76%

Section: Low Serum Concentrations Of Total 25-hydroxyvitamin D (25[oh]d)mentioning

confidence: 99%

Section: Low Serum Concentrations Of Total 25-hydroxyvitamin D (25[oh]d)mentioning

confidence: 99%

See 1 more Smart Citation

Critically Ill Children Have Low Vitamin D Binding Protein, Influencing Bioavailability of Vitamin D

Madden¹,

Feldman²,

Chun³

et al. 2015

Annals ATS

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“…Finally, C5a/C5a des Arg binding (amino acids 126e175) and plasma membrane binding domains (amino acids 150e172 and amino acids 379e402) have been identified [16]. Serum concentration 300e600 mg/L acute injury or sepsis: a decrease in the serum DBP concentration of 50e120 mg/L [27,28] Half-life Actin-free DBP: 12e24 h, actin-bound DBP: ±30 min [75] Diverse physiologically important properties have been attributed to DBP (Fig. 1).…”

Section: Introductionmentioning

confidence: 96%

Behind the scenes of vitamin D binding protein: More than vitamin D binding

Delanghe

Speeckaert

2015

Best Practice & Research Clinical Endocrinology & Metab

145

124

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“…Recent investigation has revealed vitamin D-binding protein (DBP), also known as Gc-globulin, is an acute phase reactant which falls in the event of acute disease. Dhal, et al [39] reported that it decreased acutely to 87 % of baseline value following surgery, suggesting that acute situations potentially result in acutely low 25-OH-D even in a patient with reasonable body stores. Although 88% of 25-OH-D is bound to this protein in the serum [40], only 5% of the binding sites are normally occupied on the circulating DPB.…”

Section: Discussionmentioning

confidence: 99%

Vitamin D Deficiency as an Ignored Cause of Hypocalcemia in Acute Illness: Report of 2 Cases and Review of Literature

Noto¹,

Heller²

2009

TOEJ

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Abstract:We describe the clinical and laboratory findings in 2 cases of hypocalcemia secondary to vitamin D deficiency in intensive care unit and the response of calcium to treatment. We also discuss the mechanism and review pertinent literature. The first patient was admitted due to stroke. Laboratory data included serum calcium 7.6 mg/dl, intact parathyroid hormone (PTH) 891.6 pg/ml, 25-hydroxyvitamin D (25-OH-D) 7 ng/ml (17.5 nmol/l), 1,25-dihydroxyvitamin D (1,25-OH-D) 43 pg/ml (103.2 nmol/l), and corrected QT (QTc) interval 494 msec. After two weeks of treatment with oral calcium and ergocalciferol, serum calcium and intact PTH levels and QTc interval normalized. The second patient was transferred for the management of disseminated cytomegalovirus infection. Laboratory work-up revealed serum calcium 7.7 mg/dl, creatinine 4.3 mg/dl, intact PTH 207.5 pg/ml, 25-OH-D <5 ng/ml (<12.5 nmol/l), 1,25-OH-D <10 pg/ml (<24 nmol/l), and QTc interval 505 msec. After treatment for vitamin D deficiency and infection, we observed normalization of creatinine, corrected calcium, intact PTH and QTc interval. The clinical courses were uneventful in both cases. In conclusion, we would like to emphasize that vitamin D status should be evaluated in patients with hypocalcemia in acute settings because vitamin D deficiency is common and readily treatable, and there may be clear life-threatening consequences if it is not treated.

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Gc-globulin is an acute phase reactant and an indicator of muscle injury after spinal surgery

Cited by 31 publications

References 37 publications

Critically Ill Children Have Low Vitamin D Binding Protein, Influencing Bioavailability of Vitamin D

Critically Ill Children Have Low Vitamin D Binding Protein, Influencing Bioavailability of Vitamin D

Behind the scenes of vitamin D binding protein: More than vitamin D binding

Vitamin D Deficiency as an Ignored Cause of Hypocalcemia in Acute Illness: Report of 2 Cases and Review of Literature

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