Correspondence
Volume 162 Number 5
operative procedures probably result in elevated levels of CA 125 during the postoperative period. However, another possibility is that the metabolic activity during pregnancy differs from that in ovarian tumor bearing women or the structure of CA 125 released from the decidua differs from that in ovarian tumor. Norimasa Sagawa, MD Fuminori Kobayashi, MD Kousaku Nakamura, MD Masafumi Nonogaki, MD Chiaki Ban, MD Shingo Fujii, MD Takahide Mori, MD Department of Gynecology and Obstetrics Kyoto University Faculty of Medicine 54 Kawahara-cho, Shogo-in, Sakyo-ku Kyoto 606, Japan
Natural immunoglobulin M antibodies against Toxoplasma gondii during pregnancy To the Editors: Dr. Konishi reported positivity for immunoglobulin M (IgM) against Toxoplasma gondii in the absence of specific immunoglobulin G (IgG) in a pregnant woman (Konishi E. A pregnant woman with a high level of naturally occurring immunoglobulin M antibodies to Toxoplasma gondii. AM J OBSTET GYNECOL 1987;157:832-3). The author considered the antiToxoplasma antibodies of the IgM class as natural immunoglobulins and excluded in his patient the occurrence of toxoplasmic infection. Recently we observed another unusual situation in a pregnant woman whose serologic follow-up is more complete; it includes a preconceptional sample and some other specimens after delivery. The index case,
1359
a healthy 27-year-old woman, had negative results for IgG and IgM antibodies against Toxoplasma gondii when tested before pregnancy by enzyme-linked immunosorbent assay (ELISA) in September 1986. In September 1987 at 6 weeks' gestation, when she routinely repeated the ELISA for anti-Toxoplasma antibodies, she was found positive for IgM but negative for IgG. The woman was absolutely symptomless and no clinical sign of infection was evident. A second serum specimen, obtained at 8 weeks' gestation and examined in our laboratory, confirmed the presence of IgM antibodies by ELISA and immunofluorescent assay. The direct agglutination test results after treatment with 2mercaptoethanol were negative for IgG, as were the ELISA results for IgG, whereas the Sabin-Feldman dye test results were positive (31 IU/ml). Suspicion of an acute toxoplasmic infection prompted a 2 gml day spiramycin regimen that was started at week 10 and continued without stopping during the rest of the pregnancy. The above-mentioned serologic picture persisted nearly unvaried until week 18 but since week 30 antiToxoplasma IgM became undetectable and the SabinFeldman dye test titer decreased to 15 IU Iml (Table I). In all specimens, test results for rheumatoid factor and antinuclear antibodies were negative. In May 1988 at 39 weeks' gestation, the woman naturally delivered a healthy newborn. Neurologic evaluations and eyes examinations were normal at birth and during the 10 months of follow-up. In the umbilical blood, anti-Toxoplasma IgM test results were negative by ELISA; IgG results by ELISA, direct agglutination test, and dye test were also negative «7 IU/ml). Samples of cord blood and placenta gave negative results when injected intra peritoneally in mice and tissue cultures. Tested just after delivery and again 7 months later,
Table I. Serum toxoplasmic antibodies in preconceptional, gestational, and postdelivery maternal follow-up Serologic test results
Time
Direct agglutination
Direct agglutination after 2 mercaptoethanol
ELISA for IgG
8 months before pregnancy Week of pregnancy 6 8 10 14 16 18 30 39 7 months after delivery
Double sandwich ELISA for IgM
Immunofluorescent assay
Negative
Negative
1:256 1:64 1:128 1:128 1:128 1:64 1 :64
Negative Negative Negative Negative Negative Negative Negative
Negative Negative Negative Negative Negative Negative Negative Negative
Positive Positive Positive Positive Positive Positive Negative Negative
1:32
Negative
Negative
Negative
I: 32 I: 32 1:64 Negative
Sabin-Feldman dye test
31 63 63 63 63 15 15 15
1360 Correspondence
the mother had positive results only for the dye test (15 IU/ml), whereas the infant's serologic assays remained negative for anti-Toxoplasma IgG and IgM. Also in the woman we observed, it is not possible to confirm the recent toxoplasmic infection on the basis of the serologic follow-up, but unlike Konishi, we could identify a "limited" period of positivity for IgM against Toxoplasma that covers at least the first 18 weeks of pregnancy. In our case the positivity for anti-Toxoplasma IgM might be a result of natural antibodies induced by nontoxoplasmic antigens of placental origin or by other unidentified stimuli. It is known that toxoplasmic membrane antigens may cross-react with natural antibodies in patients who have never been infected with Toxoplasma, I. 2 but it is significant to note that natural antibodies may also influence highly specific serologic tests (ELISA for IgM and the dye test) for toxoplasmosIs. Because an acute toxoplasmic infection cannot be confirmed in the absence of increasing IgG titers in subjects suspected of recent infection, the dynamic study of humoral response to Toxoplasma gondii must be carefully evaluated, especially during pregnancy when a certain and early diagnosis is required. We thank Professor G. Desmonts for the authoritative supervision of this case. Nadia Gussetti, MD Ruggiero D'Elia, MD Department of Pediatrics University of Padova Via Giustiniani 3 Padova, Italy 35128 Attilio Mottola, MD Egidio Rigoli, MD Institute of Microbiology S. Maria dei Battuti Hospital Ca'Foncello Treviso, Italy 31100 REFERENCES 1. Desmonts G, Baufine-Ducrocq H, Couzinequ P, Peloux Y. Nouv Presse Med 1974;3:1547-9. 2. Potasman I, Araujo FG, Remington jS. j Clin Microbiol 1986;24:1050-4.
Reply To the Editors: I appreciate the interest of Dr. Gussetti and her colleagues in my work. They provided another case of a pregnant woman with high levels of naturally occurring immunoglobulin M (lgM) antibodies against Toxoplasma gondii. Serologic tests indicated positive results for IgM antibodies from 6 through 18 weeks' gestation, but IgG antibodies were consistently negative throughout the study period. Their report clearly shows that we cannot diagnose recent Toxoplasma infection from only the data of IgM antibodies. The detailed study of humoral immune responses to an acquired infection with this par-
May 1990 Am J Obstet Gynecol
asite, especially in symptom-free cases, will be needed for serodiagnosis of Toxoplasma infection during pregnancy. Our recent surveys of natural IgM antibodies among Japanese populations revealed that a small but significant number of people had such high levels of IgM antibodies to Toxoplasma gondii without a subsequent increase in IgG antibody level (rheumatoid factor and antinuclear antibodies were also negative). When paired sera collected at a I-year interval were tested for IgM antibodies, changes ~0.1 in enzyme-linked immunosorbent assay value was observed only in about 13% of the population, and no pairs showed changes ~0.2. Another serum population obtained over 4 years at yearly intervals also showed almost constant natural IgM antibody levels without any considerable changes. Moreover, similar frequency distribution patterns of IgM antibody levels were obtained in populations of pregnant and general women. In this sense, the reported case by Dr. Gussetti et al. in which positive IgM antibody levels were observed during the limited period may be rare and significant. Eiji Konishi, PhD Department of Medical Zoology Kobe University School of Medicine Kobe 650, Japan Endometrial involution To the Editors: We were particularly interested III the article of Check et al. (Check JH, Shanis BS, Stanley C, Chase JS, Nazari A, Wu CH. Amenorrhea in an ovulatory woman despite a normal uterine cavity: Case report. AMJ OBSTET GYNECOL 1989;160:598-9). We reported a similar observation in 1966 in a study on the menstrual endometrium. 1 The woman was 27 years old and, although she had secondary amenorrhea when she was first seen, she had four normal pregnancies. We believe that such cases favor an endometrial involution without associated tissue shedding. We think, in fact, that during normal menstruation the endometrium essentially undergoes a process of regression with reorganization and that tissue shedding is minimal or inconstant. 2 J. Ritter, MD Service de Gynecologie-Obstetrique I CHRU Strasbourg-Hopital de Hautepierre Avenue Moli'agere 67098 Strasbourg Cedex, France E. Philippe, MD Institut d'Anatomie Pathologique CHRU Strasbourg-BP 22 1 Place de I'Hopital 67064 Strasbourg Cedex, France REFERENCES 1. Philippe E, Ritter j, Gandar R. L'endometre biphasique normal en periode menstruelle. Gynecol Obstet (Paris) 1966;65:515-31. 2. Ritter j, Philippe E. La menstruation normale. Encyclo-
Volume 162 Number 5
operative procedures probably result in elevated levels of CA 125 during the postoperative period. However, another possibility is that the metabolic activity during pregnancy differs from that in ovarian tumor bearing women or the structure of CA 125 released from the decidua differs from that in ovarian tumor. Norimasa Sagawa, MD Fuminori Kobayashi, MD Kousaku Nakamura, MD Masafumi Nonogaki, MD Chiaki Ban, MD Shingo Fujii, MD Takahide Mori, MD Department of Gynecology and Obstetrics Kyoto University Faculty of Medicine 54 Kawahara-cho, Shogo-in, Sakyo-ku Kyoto 606, Japan
Natural immunoglobulin M antibodies against Toxoplasma gondii during pregnancy To the Editors: Dr. Konishi reported positivity for immunoglobulin M (IgM) against Toxoplasma gondii in the absence of specific immunoglobulin G (IgG) in a pregnant woman (Konishi E. A pregnant woman with a high level of naturally occurring immunoglobulin M antibodies to Toxoplasma gondii. AM J OBSTET GYNECOL 1987;157:832-3). The author considered the antiToxoplasma antibodies of the IgM class as natural immunoglobulins and excluded in his patient the occurrence of toxoplasmic infection. Recently we observed another unusual situation in a pregnant woman whose serologic follow-up is more complete; it includes a preconceptional sample and some other specimens after delivery. The index case,
1359
a healthy 27-year-old woman, had negative results for IgG and IgM antibodies against Toxoplasma gondii when tested before pregnancy by enzyme-linked immunosorbent assay (ELISA) in September 1986. In September 1987 at 6 weeks' gestation, when she routinely repeated the ELISA for anti-Toxoplasma antibodies, she was found positive for IgM but negative for IgG. The woman was absolutely symptomless and no clinical sign of infection was evident. A second serum specimen, obtained at 8 weeks' gestation and examined in our laboratory, confirmed the presence of IgM antibodies by ELISA and immunofluorescent assay. The direct agglutination test results after treatment with 2mercaptoethanol were negative for IgG, as were the ELISA results for IgG, whereas the Sabin-Feldman dye test results were positive (31 IU/ml). Suspicion of an acute toxoplasmic infection prompted a 2 gml day spiramycin regimen that was started at week 10 and continued without stopping during the rest of the pregnancy. The above-mentioned serologic picture persisted nearly unvaried until week 18 but since week 30 antiToxoplasma IgM became undetectable and the SabinFeldman dye test titer decreased to 15 IU Iml (Table I). In all specimens, test results for rheumatoid factor and antinuclear antibodies were negative. In May 1988 at 39 weeks' gestation, the woman naturally delivered a healthy newborn. Neurologic evaluations and eyes examinations were normal at birth and during the 10 months of follow-up. In the umbilical blood, anti-Toxoplasma IgM test results were negative by ELISA; IgG results by ELISA, direct agglutination test, and dye test were also negative «7 IU/ml). Samples of cord blood and placenta gave negative results when injected intra peritoneally in mice and tissue cultures. Tested just after delivery and again 7 months later,
Table I. Serum toxoplasmic antibodies in preconceptional, gestational, and postdelivery maternal follow-up Serologic test results
Time
Direct agglutination
Direct agglutination after 2 mercaptoethanol
ELISA for IgG
8 months before pregnancy Week of pregnancy 6 8 10 14 16 18 30 39 7 months after delivery
Double sandwich ELISA for IgM
Immunofluorescent assay
Negative
Negative
1:256 1:64 1:128 1:128 1:128 1:64 1 :64
Negative Negative Negative Negative Negative Negative Negative
Negative Negative Negative Negative Negative Negative Negative Negative
Positive Positive Positive Positive Positive Positive Negative Negative
1:32
Negative
Negative
Negative
I: 32 I: 32 1:64 Negative
Sabin-Feldman dye test
31 63 63 63 63 15 15 15
1360 Correspondence
the mother had positive results only for the dye test (15 IU/ml), whereas the infant's serologic assays remained negative for anti-Toxoplasma IgG and IgM. Also in the woman we observed, it is not possible to confirm the recent toxoplasmic infection on the basis of the serologic follow-up, but unlike Konishi, we could identify a "limited" period of positivity for IgM against Toxoplasma that covers at least the first 18 weeks of pregnancy. In our case the positivity for anti-Toxoplasma IgM might be a result of natural antibodies induced by nontoxoplasmic antigens of placental origin or by other unidentified stimuli. It is known that toxoplasmic membrane antigens may cross-react with natural antibodies in patients who have never been infected with Toxoplasma, I. 2 but it is significant to note that natural antibodies may also influence highly specific serologic tests (ELISA for IgM and the dye test) for toxoplasmosIs. Because an acute toxoplasmic infection cannot be confirmed in the absence of increasing IgG titers in subjects suspected of recent infection, the dynamic study of humoral response to Toxoplasma gondii must be carefully evaluated, especially during pregnancy when a certain and early diagnosis is required. We thank Professor G. Desmonts for the authoritative supervision of this case. Nadia Gussetti, MD Ruggiero D'Elia, MD Department of Pediatrics University of Padova Via Giustiniani 3 Padova, Italy 35128 Attilio Mottola, MD Egidio Rigoli, MD Institute of Microbiology S. Maria dei Battuti Hospital Ca'Foncello Treviso, Italy 31100 REFERENCES 1. Desmonts G, Baufine-Ducrocq H, Couzinequ P, Peloux Y. Nouv Presse Med 1974;3:1547-9. 2. Potasman I, Araujo FG, Remington jS. j Clin Microbiol 1986;24:1050-4.
Reply To the Editors: I appreciate the interest of Dr. Gussetti and her colleagues in my work. They provided another case of a pregnant woman with high levels of naturally occurring immunoglobulin M (lgM) antibodies against Toxoplasma gondii. Serologic tests indicated positive results for IgM antibodies from 6 through 18 weeks' gestation, but IgG antibodies were consistently negative throughout the study period. Their report clearly shows that we cannot diagnose recent Toxoplasma infection from only the data of IgM antibodies. The detailed study of humoral immune responses to an acquired infection with this par-
May 1990 Am J Obstet Gynecol
asite, especially in symptom-free cases, will be needed for serodiagnosis of Toxoplasma infection during pregnancy. Our recent surveys of natural IgM antibodies among Japanese populations revealed that a small but significant number of people had such high levels of IgM antibodies to Toxoplasma gondii without a subsequent increase in IgG antibody level (rheumatoid factor and antinuclear antibodies were also negative). When paired sera collected at a I-year interval were tested for IgM antibodies, changes ~0.1 in enzyme-linked immunosorbent assay value was observed only in about 13% of the population, and no pairs showed changes ~0.2. Another serum population obtained over 4 years at yearly intervals also showed almost constant natural IgM antibody levels without any considerable changes. Moreover, similar frequency distribution patterns of IgM antibody levels were obtained in populations of pregnant and general women. In this sense, the reported case by Dr. Gussetti et al. in which positive IgM antibody levels were observed during the limited period may be rare and significant. Eiji Konishi, PhD Department of Medical Zoology Kobe University School of Medicine Kobe 650, Japan Endometrial involution To the Editors: We were particularly interested III the article of Check et al. (Check JH, Shanis BS, Stanley C, Chase JS, Nazari A, Wu CH. Amenorrhea in an ovulatory woman despite a normal uterine cavity: Case report. AMJ OBSTET GYNECOL 1989;160:598-9). We reported a similar observation in 1966 in a study on the menstrual endometrium. 1 The woman was 27 years old and, although she had secondary amenorrhea when she was first seen, she had four normal pregnancies. We believe that such cases favor an endometrial involution without associated tissue shedding. We think, in fact, that during normal menstruation the endometrium essentially undergoes a process of regression with reorganization and that tissue shedding is minimal or inconstant. 2 J. Ritter, MD Service de Gynecologie-Obstetrique I CHRU Strasbourg-Hopital de Hautepierre Avenue Moli'agere 67098 Strasbourg Cedex, France E. Philippe, MD Institut d'Anatomie Pathologique CHRU Strasbourg-BP 22 1 Place de I'Hopital 67064 Strasbourg Cedex, France REFERENCES 1. Philippe E, Ritter j, Gandar R. L'endometre biphasique normal en periode menstruelle. Gynecol Obstet (Paris) 1966;65:515-31. 2. Ritter j, Philippe E. La menstruation normale. Encyclo-
