Macroprolactin in mothers and their babies: what is its origin?

Norito Nishiyama; Naoki Hattori; Kohozo Aisaka; Masayuki Ishihara; Takanori Saito

doi:10.1515/cclm-2024-0235

Enjoy 40% off

academic books on De Gruyter Brill *

Article

Macroprolactin in mothers and their babies: what is its origin?

Norito Nishiyama , Naoki Hattori , Kohozo Aisaka , Masayuki Ishihara and Takanori Saito

Published/Copyright: April 30, 2024

Published by

Become an author with De Gruyter Brill

Submit Manuscript Author Information

From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 62 Issue 11

Abstract

Objectives

Macroprolactinemia is one of the major causes of hyperprolactinemia. The aim of this study was to clarify the origin of macroprolactin (macro-PRL).

Methods

We examined macro-PRL in the sera of 826 pregnant women and in those of their babies’ umbilical cords at delivery. Macro-PRL was evaluated by precipitation with polyethylene glycol (PEG), gel filtration chromatography (GFC), and absorption with protein G (PG).

Results

We detected macro-PRL in 16 out of the 826 pregnant women (1.94 %) and in 14 of their babies, which may indicate the possibility of hereditary origin of macro-PRL. However, the macro-PRL ratios of the babies correlated positively with those of their mothers (r=0.72 for GFC, p<0.001 and r=0.77 for PG, p<0.001), suggesting that the immunoglobulin (Ig)G-type anti-PRL autoantibodies might be actively transferred to babies via the placenta and form macro-PRL by binding to their babies’ PRL or PRL-IgG complexes may possibly pass through the placenta. There were two cases in which only mothers had macro-PRL, indicating that the mothers had autoantibodies that did not pass through the placenta, such as IgA, PRL bound to the other proteins or PRL aggregates. No cases were found in which only the babies had macro-PRL and their mothers did not, suggesting that macro-PRL might not arise by non-hereditary congenital causes.

Conclusions

Macro-PRL in women of reproductive age might be mostly IgG-type anti-PRL autoantibody-bound PRL. The likely origin of macro-PRL in babies is the transplacental transfer of IgG-type anti-PRL autoantibodies or PRL-IgG complexes from the mothers to their babies.

Keywords: macroprolactin; macroprolactinemia; hyperprolactinemia; umbilical cord; laboratory tests

Corresponding author: Naoki Hattori, MD, PhD, Department of Orthopedic Surgery, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka, 573-1010, Japan, E-mail: hattorin@hirakata.kmu.ac.jp

Acknowledgments

We thank Ami Sudo for helping with the PRL assay for the clinical samples and Geoff Gillespie for assisting with the English writing of this manuscript.

Research ethics: The research related to human use has complied with all the relevant national regulations, institutional policies, and in accordance with the tenets of the Helsinki Declaration, and has been approved by the authors’ Institutional Review Board or equivalent committee (The Clinical Research Review Board of the Hamada Obstetrics and Gynecology Hospital, HMH 2018-02).
Informed consent: Informed consent was obtained from all individuals included in this study.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: Authors state no conflict of interest.
Research funding: None declared.
Data availability: The raw data can be obtained on request from the corresponding author.

References

1. Bjøro, T, Mørkrid, L, Wergeland, R, Turter, A, Kvistborg, A, Sand, T, et al.. Frequency of hyperprolactinaemia due to large molecular weight prolactin (150–170 kD PRL). Scand J Clin Lab Invest 1995;55:139–47. https://doi.org/10.3109/00365519509089606.Search in Google Scholar PubMed

2. Fahie-Wilson, MN, Soule, SG. Macroprolactinaemia: contribution to hyperprolactinaemia in a district general hospital and evaluation of a screening test based on precipitation with polyethylene glycol. Ann Clin Biochem 1997;34:252–8. https://doi.org/10.1177/000456329703400305.Search in Google Scholar PubMed

3. Leslie, H, Courtney, CH, Bell, PM, Hadden, DR, McCance, DR, Ellis, PK, et al.. Laboratory and clinical experience in 55 patients with macroprolactinemia identified by a simple polyethylene glycol precipitation method. J Clin Endocrinol Metab 2001;86:2743–6. https://doi.org/10.1210/jc.86.6.2743.Search in Google Scholar

4. Vallette-Kasic, S, Morange-Ramos, I, Selim, A, Gunz, G, Morange, S, Enjalbert, A., et al.. Macroprolactinemia revisited: a study on 106 patients. J Clin Endocrinol Metab 2002;87:581–8. https://doi.org/10.1210/jc.87.2.581.Search in Google Scholar

5. Gibney, J, Smith, TP, McKenna, TJ. Clinical relevance of macroprolactin. Clin Endocrinol 2005;62:633–43. https://doi.org/10.1111/j.1365-2265.2005.02243.x.Search in Google Scholar PubMed

6. Hattori, N, Ishihara, T, Saiki, Y. Macroprolactinaemia: prevalence and aetiologies in a large group of hospital workers. Clin Endocrinol 2009;71:702–8. https://doi.org/10.1111/j.1365-2265.2009.03570.x.Search in Google Scholar PubMed

7. Fahie-Wilson, MN, John, R, Ellis, AR. Macroprolactin; high molecular mass forms of circulating prolactin. Ann Clin Biochem 2005;42:175–92. https://doi.org/10.1258/0004563053857969.Search in Google Scholar PubMed

8. Soh, NAAC, Yaacob, NM, Omar, J, Jelani, AM, Shafii, N, Ismail, TST, et al.. Global prevalence of macroprolactinemia among patients with hyperprolactinemia: a systematic review and meta-analysis. Int J Environ Res Publ Health 2020;17:8199. https://doi.org/10.3390/ijerph17218199.Search in Google Scholar PubMed PubMed Central

9. Hattori, N, Inagaki, C. Anti-prolactin (PRL) autoantibodies cause asymptomatic hyperprolactinemia: bioassay and clearance studies of PRL-immunoglobulin G complex. J Clin Endocrinol Metab 1997;82:3107–10. https://doi.org/10.1210/jc.82.9.3107.Search in Google Scholar

10. Hattori, N, Nakayama, Y, Kitagawa, K, Ishihara, T, Saiki, Y, Inagaki, C. Anti-prolactin (PRL) autoantibodies suppress PRL bioactivity in patients with macroprolactinaemia. Clin Endocrinol 2008;68:72–6. https://doi.org/10.1111/j.1365-2265.2007.03001.x.Search in Google Scholar PubMed

11. Leaños-Miranda, A, Cárdenas-Mondragón, G, Rivera-Leaños, R, Ulloa-Aguirre, A, Goffin, V. Application of new homologous in vitro bioassays for human lactogens to assess the actual bioactivity of human prolactin isoforms in hyperprolactinaemic patients. Clin Endocrinol 2006;65:146–53. https://doi.org/10.1111/j.1365-2265.2006.02548.x.Search in Google Scholar PubMed

12. Fahie-Wilson, MN, Cobbaert, CM, Horvath, AR, Smith, TP. Interference by macroprolactin in assays for prolactin: will the in vitro diagnostics regulation lead to a solution at last? Clin Chem Lab Med 2022;60:1350–5. https://doi.org/10.1515/cclm-2022-0460.Search in Google Scholar PubMed

13. Schiettecatte, J, De Schepper, J, Velkeniers, B, Smitz, J, Van Steirteghem, A. Rapid detection of macroprolactin in the form of prolactin-immunoglobulin G complexes by immunoprecipitation with anti-human IgG-agarose. Clin Chem Lab Med 2001;39:1244–8. https://doi.org/10.1515/cclm.2001.200.Search in Google Scholar PubMed

14. De Schepper, J, Schiettecatte, J, Velkeniers, B, Blumenfeld, Z, Shteinberg, M, Devroey, P, et al.. Clinical and biological characterization of macroprolactinemia with and without prolactin-IgG complexes. Eur J Endocrinol 2003;149:201–7. https://doi.org/10.1530/eje.0.1490201.Search in Google Scholar PubMed

15. Amadori, P, Dilberis, C, Marcolla, A, Pinamonti, M, Menapace, P, Valentini, A. Identification of IgG-immunocomplex macroprolactin with an immunometric “sandwich” system: technical and clinical considerations. J Endocrinol Invest 2004;27:1022–8. https://doi.org/10.1007/bf03345304.Search in Google Scholar

16. Hattori, N, Ikekubo, K, Nakayama, Y, Kitagawa, K, Inagaki, C. Immunoglobulin G subclasses and prolactin (PRL) isoforms in macroprolactinemia due to anti-PRL autoantibodies. J Clin Endocrinol Metab 2005;90:3036–44. https://doi.org/10.1210/jc.2004-1600.Search in Google Scholar PubMed

17. Yu, C, Fan, F, Hu, S, Meng, L, Xu, D, Wang, J, et al.. Evaluation of autoantibodies and immunoglobulin G subclasses in women with suspected macroprolactinemia. J Clin Lab Anal 2020;34:e23456. https://doi.org/10.1002/jcla.23456.Search in Google Scholar PubMed PubMed Central

18. Jackson, RD, Wortsman, J, Malarkey, WB. Persistence of large molecular weight prolactin secretion during pregnancy in women with macroprolactinemia and its presence in fetal cord blood. J Clin Endocrinol Metab 1989;68:1046–50. https://doi.org/10.1210/jcem-68-6-1046.Search in Google Scholar PubMed

19. Larrea, F, Escorza, A, Valero, A, Hernandez, L, Cravioto, MC, Diaz-Sanchez, V. Heterogeneity of serum prolactin throughout the menstrual cycle and pregnancy in hyperprolactinemic women with normal ovarian function. J Clin Endocrinol Metab 1989;68:982–7. https://doi.org/10.1210/jcem-68-5-982.Search in Google Scholar PubMed

20. Hattori, N, Aisaka, K, Shimatsu, A. A possible cause of the variable detectability of macroprolactin by different immunoassay systems. Clin Chem Lab Med 2016;54:603–8. https://doi.org/10.1515/cclm-2015-0484.Search in Google Scholar PubMed

21. Aubert, ML, Grumbach, MM, Kaplan, SL. The ontogenesis of human fetal hormones. III. Prolactin. J Clin Invest 1975;56:155–64. https://doi.org/10.1172/jci108064.Search in Google Scholar PubMed PubMed Central

22. Malek, A, Sager, R, Schneider, H. Transport of proteins across the human placenta. Am J Reprod Immunol 1998;40:347–51. https://doi.org/10.1111/j.1600-0897.1998.tb00064.x.Search in Google Scholar PubMed

23. Srinivasan, J, Lancaster, JN, Singarapu, N, Hale, LP, Ehrlich, LIR, Richie, ER. Age-related changes in thymic central tolerance. Front Immunol 2021;12:676236. https://doi.org/10.3389/fimmu.2021.676236.Search in Google Scholar PubMed PubMed Central

24. Smith, TP, Kelly, S, Fahie-Wilson, MN. Cross-reactivity in assays for prolactin and optimum screening policy for macroprolactinaemia. Clin Chem Lab Med 2022;60:1365–72. https://doi.org/10.1515/cclm-2022-0459.Search in Google Scholar PubMed

25. Levinson, SS, Miller, JJ. Towards a better understanding of heterophile (and the like) antibody interference with modern immunoassays. Clin Chim Acta 2002;325:1–15. https://doi.org/10.1016/s0009-8981(02)00275-9.Search in Google Scholar PubMed

26. Freeman, ME, Kanyicska, B, Lerant, A, Nagy, G. Prolactin: structure, function, and regulation of secretion. Physiol Rev 2000;80:1523–631. https://doi.org/10.1152/physrev.2000.80.4.1523.Search in Google Scholar PubMed

Received: 2024-02-21

Accepted: 2024-04-22

Published Online: 2024-04-30

Published in Print: 2024-10-28

You are currently not able to access this content.

Articles in the same Issue

https://doi.org/10.1515/cclm-2024-0235

Keywords for this article

macroprolactin; macroprolactinemia; hyperprolactinemia; umbilical cord; laboratory tests