摘要:

SummaryA 4-year study of a boy with combined immune deficiency is presented, and the impact of this disease on various aspects of his growth and development is examined. There is no evidence of immune deficiency in either parent or in the genetic background on the maternal side. Three children of a brother of the mother's father may have had immune deficiencies but two have grown to be teenagers with no problems. Another died. At autopsy, however, lymph nodes appeared normal. The deceased older brother had severe combined immune deficiency (SCID). The autopsy findings showedPneumocystis cariniipneumonia to be the direct cause of death and these findings contributed to the diagnosis of SCID. After a successful germ-free birth, the male infant (DV) was placed in the isolator. Laboratory tests were normal except that the x-rays showed no thymic shadow, his absolute lymphocyte count ranged from 399–440/mm, and the lymphocytes showed no proliferative response to phytohemagglutinin (PHA). Specific tests showed the antibody-producing immune system and the cell-mediated immune system to be severely defective. The patient's lymphocytes elicited positive responses by lymphocytes from father, mother, and sister. Subsequent search in national and international tissue-typing laboratories has shown four HLA matches but none has been nonreactive in mixed lymphocyte culture (MLC). therefore, this patient has remained in isolation to the present; now he is 4 years old.Approximately 35 species of microorganisms, mostly transient contaminants, have been isolated, taking into account that the same organism may have been identified under different names in different laboratories. Those isolated frequently and in sufficiently high concentration to indicate colonization have been speciated as follows: anaerobes—Propionibacterium acnes, Lactobacillus catenaforme(disappeared spontaneously),Bacteroides oralisss.elongatus, Clostridium (perenne, hastiforme, bifermentans), Bacteroides clostridiiformisss.clostridiiformis; aerobes—Alcaligenes faecalis(eradicated by antibiotics),Staphylococcus epidermidis, Enterobacter agglomerans, Micrococcussp. subgroup 1,Bacillus pulvifaciens(disappeared spontaneously); yeasts—Candida (tropicalis, parapsilosis).Seven are considered to be probable components of the current autoflora:P. acnes, C. bifermentans, B. clostridiiformisss.clostridiiformis, S. epidermidis, Micrococcussp. subgroup 1,E. agglomerans, C. parapsilosis.No viruses or protozoa have been isolated. At age 3 years, the mean quantitation of anaerobic cells was 7.9 × 107viable cells/g feces; this falls short of the mean anaerobic load from normal children. The mean aerobic concentration was 1.2 × 108viable cells/g feces, not unlike normal children. Qualitatively his flora has abnormally few species and lacks those most common in normal subjects. This child has had no evidence of infection and has always been in excellent health even though some organisms which could be pathogenic under some circumstances have been isolated.Phagocytic functions, adenosine deaminase (ADA) levels, and serum complement levels were normal except that C1q was 30% of normal. Thymosin assays showed adult control subject 1/4, 10-year control subject 1/128, this patient 0. To age 47 months serum immunoglobulin (Ig) M levels were generally low and IgG was not detected. No serum IgA was detected until, at 39 months, assays indicated IgA at the lowest range of sensitivity of the agar plates. Ultracentrifugal analysis of serum revealed no 19s material at 24 months but at 36 months both 7s and 19s materials were present. At 44 months these fractions were still present and an abnormal 4s component had disappeared. Radial immunodiffusion assay at 44 months indicated the presence of IgD and at that time an IgM component of normal electrophoretic mobility was detected for the first time. Before injection of keyhole limpet hemocyanin (KLH) at 1 month antibody liter was 0–0. Antibody titers and skin tests after injection were negative and remained so after further antigen injections. At 11 months, on the fifth rechallenge, the patient had an erythematous reaction of 5 mm diameter but no significant antibody responses. Two typhoid antigen injections elicited no antibody response. Using the isolated leukocyte technique, lymphocytes showed minimal or no blastogenesis in response to PHA, poke-weed mitogen (PWM), or in MLC. Using the whole blood technique, transient, low positive responses (stimulation index (SI) range 4.1–9.7) to PHA were observed but not consistently maintained. At 3 years, purified T cells showed a notable response (SI 17.4) to PHA, but this was not obtained in subsequent experiments. Transfer factor (TF) was given to this patient between 10 and 16 months of age. In skin tests toC. albicans, purified protein derivative (PPD) and streptokinase-streptodornase (SK-SD) administered a day after TF injection, small areas of redness appeared early and faded rapidly. Addition of TF to lymphocyte cultures obtained before administration of TF caused them to respond toC. albicansand PPD (SI 8 for each); after injection of TF and skin tests to these antigens, similar responsiveness could not be induced by addition of TF. After a second dose of TF, before skin test to SK-SD, the lymphocytes responded to SK-SDin vitrowith TF (SI 13) and without TF (SI 8) added to the cultures; after SK-SD skin tests, responses were no longer elicited under the same circumstances. During the first 2 years membrane-bound immunoglobulin (SmIg), bearing lymphocytes ranged from 50–100% of the total lymphocytes whereas the percentage of lymphocytes with cells forming rosettes with sheep erythrocytes (E-RFC) markers was low, about 3–12%. Between 2.5 and 4 years striking changes occurred, representing a shift toward a normal distribution (20–40% SmIg and 19–60% E-RFC). In electron microscopic studies, new type lymphocytes which appeared at 15 months increased in number until at 4 years they represented 93% of the lymphocytes. In contrast to cells from normal donors, complement (C3) receptor-bearing cells of this patient did not express significant direct cytotoxicity; however, lymphotoxin (LT) levels 3–4 times those

ISSN:0031-3998    

出版商:OVID    

年代:1977

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:1977

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:1977

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:1977

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:1977

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:1977

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:1977

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:1977

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:1977

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:1977

数据来源: OVID