1142 LCTA IN STUDY POPULATIONS
*‘ of donors whose lymphocytes were killed by test sera. sera killed ;::50( of the panel of 20 normal lym-
ft of subjects whose phocyte donors.
:):No. of sera in each group. SLE sera while 2 remained negative. The sera overall tended to kill a lower percentage of the panel than the SLE sera
(table). These data support those from family studies which showed. similar incidence of LCTA in consanguineous and non-consanguineous relatives in contact with SLE patients, although this is not a universal finding, 6.7 related, in part, to timing of exposure to the SLE patient.8 Together they strongly suggest that an agent or antigen is present in SLE that can induce antibody to lymphocytes in exposed individuals. Either exposure to serum and/or tissues or prolonged close contact with the patients seem to trigger the development of this response. In families, relatives living with the patient have a higher frequency of LCTA and positive antinuclear antibodies and positive skin fluorescence than do those with casual contact. A study of dogs with SLE demonstrated that cell-free filtrates of tissue could produce serological abnormalities in mice immunised with these filtrates.9 The mice did not develop disease, although they did produce antinuclear antibodies. Our data are analogous in that the laboratory personnel produce antibodies to DNA and LCTA with no overt disease. In contrast, we (unpublished) and others’O have found that human household contacts of dogs with SLE do not acquire serological abnormalities. Whether this agent bears a causal relationship to the disease or represents a secondary phenomenon is unclear. The heightened immune response in the SLE patient could lead to increased production of endogenous viral antigens on lymphocyte membranes since recent studies indicate that immune reactions can activate latent viruses resulting in massive production of virus and viral antigens." These antigens, either free in the serum or incorporated in the cell surface, could induce antibodies that cross-react with normal cells such as lymphocytes. The LCTA response in exposed individuals may then represent a normal response to antigens that might parellel the course of SLE but have no direct relationship to its cause. On a
6. Raum D, Glass D, Soter NA, Stillman JS, Carpenter CB, Schur PH. Lymphocytotoxic antibodies. HLA antigen associations, disease associations, and family studies. Arthritis Rheum 1977; 20: 933-36. 7. Cleland LG, Bell DA, Willans M, Saurino BC. Familial lupus. Family studies of HLA and serologic findings. Arthritis Rheum 1978; 21: 183-81. 8 Messner RP, DeHoratius RJ. Epidemiology of anti-lymphocyte antibodies in systemic lupus erythematosus. Arthritis Rheum 1978; 21: 167-70S. 9. Lewis RM, Andre-Schwartz J, Harris GS, Hirsch MS, Black PH, Schwartz RS. Canine systemic lupus erythematosus. Transmission of serologic abnormalities by cell-free filtrates. J Clin Invest 1973; 52: 1893-1907. 10 Reinertsen JL, Kasllow RA, Klippel JH, et al. An epidemiologic study of households exposed to canine systemic lupus erythematosus. Arthritis
the other hand, the transmissible agent may be capable of deregulating the immune response. Those individuals who develop SLE may be genetically unable to resist this deregulation, while most individuals can limit the disruption of their immune control to the production of a few autoantibodies. Despite the current lack of direct evidence for a bacterial or viral aetiology of SLE, these data suggest that the search for an infectious agent should not be abandoned. If the production of these serological abnormalities in individuals exposed to SLE blood is due to an agent responsible for the disease, it will be particularly important to define genetic susceptibility factors so that individuals at risk can be protected from unnecessary exposure.
Supported in part by: the Lupus Foundation of Delaware Valley, the Pennsylvania Lupus Foundation, Commonwealth of Pennsylvania, the Pew Foundation through the Arthritis Foundation, Eastern Pennsylvania Chapter, and National Institutes of Health grant lR23 AH4574. Division of
Rheumatology, Department of Medicine, Jefferson Medical College, Philadelphia, Pennsylama 19107, U.S.A.; University of New Mexico School of Medicine, Albuquerque; and National Jewish Hospital and Research Center, Denver, Colorado
RAPHAEL J. DEHORATIUS, ROBERT L. RUBIN RONALD P. MESSNER RONALD I. CARR
THE METHYLENE-BLUE BABY
SIR,-Obstetricians have injected various dyes, occasionally into the amniotic cavity to detect a leak of amniotic fluid. We have seen a case of neonatal jaundice due to a hxmolytic anaemia in an infant born to a mother investigated in this way. A 3.4 kg 7 h old female infant born after 41 weeks’ gestation was transferred to the Children’s Hospital of Philadelphia with respiratory distress. Premature rupture of the membranes had been suspected 24 h before delivery and 20 ml of a 1% solution of methylene-blue had been injected into the amniotic cavity; no leak was found. A decelerating fetal heartrate prompted csesarean section. Apgar scores were 1 at 1 min and 3 at 5 min. The infant was stained a deep blue. She was intubated and resuscitated. Direct laryngoscopy revealed the cords to be blue and meconium-stained. On transfer, the infant’s skin and oral mucosa were pale blue. In 30% oxygen, the baby had nasal flaring, grunting respirations, and intercostal retractions. The heart-rate was 120/min and regular, respiratory-rate 36/min, and systolic blood-pressure 54 mm Hg. Rales and rhonchi were heard in both lungs. The patient voided blue-green urine. Her Hb was 17.5g/dl, haematocrit 53.4%, red cell indices normal for age, and Coombs’ test negative. The chest X-ray revealed diffuse coarse densities with hyper-aeration, consistent with meconium aspiration. The peripheral blood smear showed marked poikilocytosis and fragmentation, polychromasia, and nucleated red blood-cells. A reticulocyte stain showed inclusions in 90% of the red cells. Betke and brilliant cresyl-blue preparations as well as electronmicroscopy demonstrated erythrocyte inclusions. No abnormal haemoglobins were found on electrophoresis. The plasma free Hb (normally absent) was 80 mg/dl, rising to 105 mg/dl by the second day. The P50 of the oxygen dissociation curve was 20 mm Hg (normal 19.0±2-0); the red-cell glutathione was 89.5 mg/dl RBC preincubation, with no drop after incubation with acetylphenylhydrazine ; the red cell glucose-6-phosphate dehydrogenase was 5-9 IU/ml RBC, consistent with a population of young red cells. Membrane-associated denatured Hb was 0.15% of total Hb (normal
*‘ of donors whose lymphocytes were killed by test sera. sera killed ;::50( of the panel of 20 normal lym-
ft of subjects whose phocyte donors.
:):No. of sera in each group. SLE sera while 2 remained negative. The sera overall tended to kill a lower percentage of the panel than the SLE sera
(table). These data support those from family studies which showed. similar incidence of LCTA in consanguineous and non-consanguineous relatives in contact with SLE patients, although this is not a universal finding, 6.7 related, in part, to timing of exposure to the SLE patient.8 Together they strongly suggest that an agent or antigen is present in SLE that can induce antibody to lymphocytes in exposed individuals. Either exposure to serum and/or tissues or prolonged close contact with the patients seem to trigger the development of this response. In families, relatives living with the patient have a higher frequency of LCTA and positive antinuclear antibodies and positive skin fluorescence than do those with casual contact. A study of dogs with SLE demonstrated that cell-free filtrates of tissue could produce serological abnormalities in mice immunised with these filtrates.9 The mice did not develop disease, although they did produce antinuclear antibodies. Our data are analogous in that the laboratory personnel produce antibodies to DNA and LCTA with no overt disease. In contrast, we (unpublished) and others’O have found that human household contacts of dogs with SLE do not acquire serological abnormalities. Whether this agent bears a causal relationship to the disease or represents a secondary phenomenon is unclear. The heightened immune response in the SLE patient could lead to increased production of endogenous viral antigens on lymphocyte membranes since recent studies indicate that immune reactions can activate latent viruses resulting in massive production of virus and viral antigens." These antigens, either free in the serum or incorporated in the cell surface, could induce antibodies that cross-react with normal cells such as lymphocytes. The LCTA response in exposed individuals may then represent a normal response to antigens that might parellel the course of SLE but have no direct relationship to its cause. On a
6. Raum D, Glass D, Soter NA, Stillman JS, Carpenter CB, Schur PH. Lymphocytotoxic antibodies. HLA antigen associations, disease associations, and family studies. Arthritis Rheum 1977; 20: 933-36. 7. Cleland LG, Bell DA, Willans M, Saurino BC. Familial lupus. Family studies of HLA and serologic findings. Arthritis Rheum 1978; 21: 183-81. 8 Messner RP, DeHoratius RJ. Epidemiology of anti-lymphocyte antibodies in systemic lupus erythematosus. Arthritis Rheum 1978; 21: 167-70S. 9. Lewis RM, Andre-Schwartz J, Harris GS, Hirsch MS, Black PH, Schwartz RS. Canine systemic lupus erythematosus. Transmission of serologic abnormalities by cell-free filtrates. J Clin Invest 1973; 52: 1893-1907. 10 Reinertsen JL, Kasllow RA, Klippel JH, et al. An epidemiologic study of households exposed to canine systemic lupus erythematosus. Arthritis
the other hand, the transmissible agent may be capable of deregulating the immune response. Those individuals who develop SLE may be genetically unable to resist this deregulation, while most individuals can limit the disruption of their immune control to the production of a few autoantibodies. Despite the current lack of direct evidence for a bacterial or viral aetiology of SLE, these data suggest that the search for an infectious agent should not be abandoned. If the production of these serological abnormalities in individuals exposed to SLE blood is due to an agent responsible for the disease, it will be particularly important to define genetic susceptibility factors so that individuals at risk can be protected from unnecessary exposure.
Supported in part by: the Lupus Foundation of Delaware Valley, the Pennsylvania Lupus Foundation, Commonwealth of Pennsylvania, the Pew Foundation through the Arthritis Foundation, Eastern Pennsylvania Chapter, and National Institutes of Health grant lR23 AH4574. Division of
Rheumatology, Department of Medicine, Jefferson Medical College, Philadelphia, Pennsylama 19107, U.S.A.; University of New Mexico School of Medicine, Albuquerque; and National Jewish Hospital and Research Center, Denver, Colorado
RAPHAEL J. DEHORATIUS, ROBERT L. RUBIN RONALD P. MESSNER RONALD I. CARR
THE METHYLENE-BLUE BABY
SIR,-Obstetricians have injected various dyes, occasionally into the amniotic cavity to detect a leak of amniotic fluid. We have seen a case of neonatal jaundice due to a hxmolytic anaemia in an infant born to a mother investigated in this way. A 3.4 kg 7 h old female infant born after 41 weeks’ gestation was transferred to the Children’s Hospital of Philadelphia with respiratory distress. Premature rupture of the membranes had been suspected 24 h before delivery and 20 ml of a 1% solution of methylene-blue had been injected into the amniotic cavity; no leak was found. A decelerating fetal heartrate prompted csesarean section. Apgar scores were 1 at 1 min and 3 at 5 min. The infant was stained a deep blue. She was intubated and resuscitated. Direct laryngoscopy revealed the cords to be blue and meconium-stained. On transfer, the infant’s skin and oral mucosa were pale blue. In 30% oxygen, the baby had nasal flaring, grunting respirations, and intercostal retractions. The heart-rate was 120/min and regular, respiratory-rate 36/min, and systolic blood-pressure 54 mm Hg. Rales and rhonchi were heard in both lungs. The patient voided blue-green urine. Her Hb was 17.5g/dl, haematocrit 53.4%, red cell indices normal for age, and Coombs’ test negative. The chest X-ray revealed diffuse coarse densities with hyper-aeration, consistent with meconium aspiration. The peripheral blood smear showed marked poikilocytosis and fragmentation, polychromasia, and nucleated red blood-cells. A reticulocyte stain showed inclusions in 90% of the red cells. Betke and brilliant cresyl-blue preparations as well as electronmicroscopy demonstrated erythrocyte inclusions. No abnormal haemoglobins were found on electrophoresis. The plasma free Hb (normally absent) was 80 mg/dl, rising to 105 mg/dl by the second day. The P50 of the oxygen dissociation curve was 20 mm Hg (normal 19.0±2-0); the red-cell glutathione was 89.5 mg/dl RBC preincubation, with no drop after incubation with acetylphenylhydrazine ; the red cell glucose-6-phosphate dehydrogenase was 5-9 IU/ml RBC, consistent with a population of young red cells. Membrane-associated denatured Hb was 0.15% of total Hb (normal
