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IgM Antibody to Treponema pallidum in Cerebrospinal Fluid of Infants With Congenital Syphilis FREE

Pablo J. Sánchez, MD; George D. Wendel, MD; Michael V. Norgard, PhD
[+] Author Affiliations

Accepted for publication June 10, 1992.

Presented in part at the 28th Interscience Conference on Antimicrobial Agents and Chemotherapy, Los Angeles, Calif, October 25, 1988.

Reprint requests to the Department of Pediatrics, UT Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75235 (Dr Sánchez).


Am J Dis Child. 1992;146(10):1171-1175. doi:10.1001/archpedi.1992.02160220057022.
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• Objectives.  —To characterize the neonatal IgG and IgM response to specific Treponema pallidum antigens in the cerebrospinal fluid (CSF) of infants with congenital syphilis.

Design.  —Cross-sectional survey.

Setting.  —Newborn nursery and neonatal intensive care unit of a county hospital in Dallas, Tex.

Participants.  —Twenty-one infants born to mothers with reactive serologic tests for syphilis were enrolled. Group 1 consisted of six infants with clinical and laboratory evidence of congenital syphilis; group 2, six asymptomatic infants born to mothers with untreated syphilis; and group 3, nine asymptomatic infants whose mothers were treated for syphilis before delivery.

Selection Procedures.  —Random sample.

Measurements and Results.  —Immunoblotting was used to examine the IgM and IgG reactivities of neonatal serum and CSF against T pallidum antigens. Among serum samples of all group 1 infants, a specific IgM response to T pallidum antigens with apparent molecular masses of 47, 45, and 17 kd was observed. Cerebrospinal fluid IgM reactivity to a 47-kd antigen of T pallidum was seen in four group 1 infants. Serum samples from two group 2 and three group 3 infants demonstrated IgM reactivity against the 47-kd antigen and, in some cases, against the 45-kd antigen of T pallidum. None of 15 group 2 and 3 infants had a positive CSF IgM immunoblot result. The IgG reactivity in CSF was similar in the three groups and was directed against T pallidum antigens with apparent molecular masses of 72, 59, 47, 45, 42, 37, 34, 17, and 15 kd.

Conclusions.  —A specific IgM response to T pallidum antigens, particularly the 47-kd antigen, was detected in the CSF of some infants with clinical and laboratory evidence of congenital syphilis. The potential usefulness of this test for the diagnosis of congenital neurosyphilis merits further study.(AJDC. 1992;146:1171-1175)

REFERENCES

Platou RV.  Treatment of congenital syphilis . Adv Pediatr. 1949;;4:39-81.
Ingall D, Dobson SM, Musher D.  Syphilis . In: Remington JS, Klein JO, eds. Infectious Diseases of the Fetus and Newborn Infant. 3rd ed. Philadelphia, Pa: WB Saunders Co; 1990;:367-394.
Thorley JD, Holmes RK, Kaplan JM, McCracken GH, Sanford JP.  Passive transfer of antibodies of maternal origin from blood to cerebrospinal fluid in infants . Lancet . 1975;;1:651-653.
Sánchez PJ, McCracken GH, Wendel GD, Olsen K, Threlkeld N, Norgard MV.  Molecular analysis of the fetal IgM response to Treponema pallidum antigens: implications for improved serodiagnosis of congenital syphilis . J Infect Dis. 1989;;159:508-517.
Sánchez PJ, Wendel GD, McCracken GH, Norgard MV.  Fetal IgM response to Treponema pallidum (TP) antigens in asymptomatic infants with suspected congenital syphilis . Pediatr Res. 1989;;25:281A. Abstract.
Lewis LL, Taber LH, Baughn RE.  Evaluation of Immunoglobulin M Western blot analysis in the diagnosis of congenital syphilis . J Clin Microbiol. 1990;;28:296-302.
Robertson SM, Kettman JR, Miller JN, Norgard MV.  Murine monoclonal antibodies specific for virulent Treponema pallidum (Nichols) . Infect Immun. 1982;;36:1076-1085.
Hanff PA, Norris SJ, Lovett MA, Miller JN.  Purification of Treponema pallidum, Nichols strain, by Percoll density gradient centrifugation . Sex Transm Dis. 1984;;11:275-286.
Lukehart SA, Hook EW, Baker-Zander SA, Collier AC, Critchlow CW, Handsfield HH.  Invasion of the central nervous system by Treponema pallidum: implications for diagnosis and treatment . Ann Intern Med. 1988;;109: 855-862.
Dobson SRM, Taber LH, Baughn RE.  Recognition of Treponema pallidum antigens by IgM and IgG antibodies in congenitally infected newborns and their mothers . J Infect Dis. 1988;;157:903-910.
Oxelius V-A, Rorsman H, Laurell A-B.  Immunoglobulins of cerebrospinal fluid in syphilis . Br J Vener Dis. 1969;;45:121-125.
Luger A, Schmidt BL, Steyrer K, Schonwald E.  Diagnosis of neurosyphilis by examination of the cerebrospinal fluid . Br J Vener Dis. 1981;;57: 232-237.
Merlin S, Andre J, Alacoque B, Paris-Hamelin A.  Importance of specific IgM antibodies in 116 patients with various stages of syphilis . Genitourin Med. 1985;;61:82-87.
Pedersen NS, Kam-Hansen S, Link H, Mavra M.  Specificity of immunoglobulins synthesized within the central nervous system in neurosyphilis . Acta Pathol Microbiol Immunol Scand Sect C. 1982;;90:97-104.
Müller F, Moskophidis M, Prange HW.  Demonstration of locally synthesized immunoglobulin M antibodies to Treponema pallidum in the central nervous system of patients with untreated neurosyphilis . J Neuroimmunol. 1984;;7:43-54.
Lee JB, Farshy CE, Hunter EF, Hambie EA, Wobig GH, Larsen SA.  Detection of immunoglobulin M in cerebrospinal fluid from syphilis patients by enzyme-linked immunosorbent assay . J Clin Microbiol. 1986;;24: 736-740.
Merlin S, Poncet F, Alacoque B, Guinet R, André J.  Treponemal antigens detected by immunoblotting with serum and CSF antibodies of neurosyphilitic patients . Ann Inst Pasteur/Microbiol. 1987;;138:709-717.
Grimprel E, Sánchez PJ, Wendel GD, et al.  Use of polymerase chain reaction and rabbit infectivity testing to detect Treponema pallidum in amniotic fluid, fetal and neonatal sera, and cerebrospinal fluid . J Clin Microbiol. 1991;;29:1711-1718.

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References

Platou RV.  Treatment of congenital syphilis . Adv Pediatr. 1949;;4:39-81.
Ingall D, Dobson SM, Musher D.  Syphilis . In: Remington JS, Klein JO, eds. Infectious Diseases of the Fetus and Newborn Infant. 3rd ed. Philadelphia, Pa: WB Saunders Co; 1990;:367-394.
Thorley JD, Holmes RK, Kaplan JM, McCracken GH, Sanford JP.  Passive transfer of antibodies of maternal origin from blood to cerebrospinal fluid in infants . Lancet . 1975;;1:651-653.
Sánchez PJ, McCracken GH, Wendel GD, Olsen K, Threlkeld N, Norgard MV.  Molecular analysis of the fetal IgM response to Treponema pallidum antigens: implications for improved serodiagnosis of congenital syphilis . J Infect Dis. 1989;;159:508-517.
Sánchez PJ, Wendel GD, McCracken GH, Norgard MV.  Fetal IgM response to Treponema pallidum (TP) antigens in asymptomatic infants with suspected congenital syphilis . Pediatr Res. 1989;;25:281A. Abstract.
Lewis LL, Taber LH, Baughn RE.  Evaluation of Immunoglobulin M Western blot analysis in the diagnosis of congenital syphilis . J Clin Microbiol. 1990;;28:296-302.
Robertson SM, Kettman JR, Miller JN, Norgard MV.  Murine monoclonal antibodies specific for virulent Treponema pallidum (Nichols) . Infect Immun. 1982;;36:1076-1085.
Hanff PA, Norris SJ, Lovett MA, Miller JN.  Purification of Treponema pallidum, Nichols strain, by Percoll density gradient centrifugation . Sex Transm Dis. 1984;;11:275-286.
Lukehart SA, Hook EW, Baker-Zander SA, Collier AC, Critchlow CW, Handsfield HH.  Invasion of the central nervous system by Treponema pallidum: implications for diagnosis and treatment . Ann Intern Med. 1988;;109: 855-862.
Dobson SRM, Taber LH, Baughn RE.  Recognition of Treponema pallidum antigens by IgM and IgG antibodies in congenitally infected newborns and their mothers . J Infect Dis. 1988;;157:903-910.
Oxelius V-A, Rorsman H, Laurell A-B.  Immunoglobulins of cerebrospinal fluid in syphilis . Br J Vener Dis. 1969;;45:121-125.
Luger A, Schmidt BL, Steyrer K, Schonwald E.  Diagnosis of neurosyphilis by examination of the cerebrospinal fluid . Br J Vener Dis. 1981;;57: 232-237.
Merlin S, Andre J, Alacoque B, Paris-Hamelin A.  Importance of specific IgM antibodies in 116 patients with various stages of syphilis . Genitourin Med. 1985;;61:82-87.
Pedersen NS, Kam-Hansen S, Link H, Mavra M.  Specificity of immunoglobulins synthesized within the central nervous system in neurosyphilis . Acta Pathol Microbiol Immunol Scand Sect C. 1982;;90:97-104.
Müller F, Moskophidis M, Prange HW.  Demonstration of locally synthesized immunoglobulin M antibodies to Treponema pallidum in the central nervous system of patients with untreated neurosyphilis . J Neuroimmunol. 1984;;7:43-54.
Lee JB, Farshy CE, Hunter EF, Hambie EA, Wobig GH, Larsen SA.  Detection of immunoglobulin M in cerebrospinal fluid from syphilis patients by enzyme-linked immunosorbent assay . J Clin Microbiol. 1986;;24: 736-740.
Merlin S, Poncet F, Alacoque B, Guinet R, André J.  Treponemal antigens detected by immunoblotting with serum and CSF antibodies of neurosyphilitic patients . Ann Inst Pasteur/Microbiol. 1987;;138:709-717.
Grimprel E, Sánchez PJ, Wendel GD, et al.  Use of polymerase chain reaction and rabbit infectivity testing to detect Treponema pallidum in amniotic fluid, fetal and neonatal sera, and cerebrospinal fluid . J Clin Microbiol. 1991;;29:1711-1718.

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