A Swedish national twin study of criminal behavior and its violent, white-collar and property subtypes.

BACKGROUND: We sought to clarify the etiological contribution of genetic and environmental factors to total criminal behavior (CB) measured as criminal convictions in men and women, and to violent (VCB), white-collar (WCCB) and property criminal behavior (PCB) in men only. METHOD: In 21 603 twin pairs from the Swedish Twin Registry, we obtained information on all criminal convictions from 1973 to 2011 from the Swedish Crime Register. Twin modeling was performed using the OpenMx package. RESULTS: For all criminal convictions, heritability was estimated at around 45% in both sexes, with the shared environment accounting for 18% of the variance in liability in females and 27% in males. The correlation of these risk factors across sexes was estimated at +0.63. In men, the magnitudes of genetic and environmental influence were similar in the three criminal conviction subtypes. However, for violent and white-collar convictions, nearly half and one-third of the genetic effects were respectively unique to that criminal subtype. About half of the familial environmental effects were unique to property convictions. CONCLUSIONS: The familial aggregation of officially recorded CB is substantial and results from both genetic and familial environmental factors. These factors are moderately correlated across the sexes suggesting that some genetic and environmental influences on criminal convictions are unique to men and to women. Violent criminal behavior and property crime are substantially influenced respectively by genetic and shared environmental risk factors unique to that criminal subtype.

The etiologic role of genetic and environmental factors in criminal behavior as determined from full- and half-sibling pairs: an evaluation of the validity of the twin method.

BACKGROUND: Twin studies have shown that criminal behavior (CB) is influenced by both genetic and shared environmental factors. Could these results be replicated using full-siblings and half-siblings? METHOD: In 911 009 full-siblings reared together (FSRT), 41 872 half-siblings reared together (HSRT) and 52 590 half-siblings reared apart (HSRA), CB was assessed from the Swedish Crime Register. Modeling, including testing for age differences and rearing status, was performed using the OpenMx package. RESULTS: Five sibling models were fitted examining FSRT and HSRT 0-2 years different in age, and both FSRT and HSRT, and FSRT, HSRT and HSRA 0-10 years different in age with and without a specified shared environment indexing age differences. Heritability estimates for CB ranged from 33 to 55% in females and 39 to 56% in males, similar to those found in our prior twin study on the same population. Estimates for the shared environment varied from 1 to 14% in females and 10 to 23% in males, lower than those estimated in the twin study. The specified shared environment indexed by sibling age differences was significant in all models tested. CONCLUSIONS: Heritability estimates for CB from full- and half-siblings closely approximated those found from twins in the same population, validating the twin method. Shared environmental estimates were lower, suggesting the presence of shared environmental factors for CB specific to twins. When rearing status can be assessed, full- and half-siblings offer an additional method for assessing the role of genetic and environmental factors in complex disorders. However, age differences in siblings may need to be included in the models.

Genetic innovation and stability in externalizing problem behavior across development: a multi-informant twin study.

The use of cross-informant ratings in previous longitudinal studies on externalizing behavior may have obscured the presence of continuity of genetic risk. The current study included latent factors representing the latent estimates of externalizing behavior based on both parent and self-report which eliminated rater-specific effects from these latent estimates. Symptoms of externalizing behavior of 1,480 Swedish twin pairs were obtained at ages 8-9, 13-14, 16-17 and 19-20 both by parent and self-report. Mx modeling was used to estimate additive genetic, shared and specific environmental influences. Genetic continuity was found over the entire developmental period as well as additional sources of genetic influence emerging around early and late adolescence. New unique environmental effects (E) on externalizing behavior arose early in adolescence. The results support both the presence of genetic continuity and change in externalizing behavior during adolescence due to newly emerging genetic and environmental risk factors.

Disentangling the causal inter-relationship between negative life events and depressive symptoms in women: a longitudinal twin study.

BACKGROUND: Negative life events are strongly associated with the development of depression. However, the etiologic relationship between life events and depression is complex. Evidence suggests that life events can cause depression, and depression increases the risk for life events. Additionally, third factors influencing both phenotypes may be involved. In this work we sought to disentangle these relationships using a genetically informative longitudinal design. METHOD: Adult female twins (n=536, including 281 twin pairs) were followed up for measurements of negative life event exposure and depressive symptoms. Four follow-ups were completed, each approximately 3 months apart. Model fitting was carried out using the Mx program. RESULTS: The best-fitting model included causal paths from life events to depressive symptoms for genetic and shared environmental risk factors, whereas paths from depressive symptoms to life events were apparent for shared environmental factors. Shared latent influence on both phenotypes was found for individual-specific effects. CONCLUSIONS: Life events and depressive symptoms have complex inter-relationships that differ across sources of variance. The results of the model, if replicated, indicate that reducing life event exposure would reduce depressive symptoms and that lowering depressive symptoms would decrease the occurrence of negative life events.

Sex differences and developmental stability in genetic and environmental influences on psychoactive substance consumption from early adolescence to young adulthood.

BACKGROUND: Genetic and environmental factors are important in the etiology of substance use. However, little is known about the stability of these factors across development. We aimed to answer three crucial questions about this etiology that have never been addressed in a single study: (1) Is there a general vulnerability to substance consumption from early adolescence to young adulthood? (2) If so, do the genetic and environmental influences on this vulnerability change across development? (3) Do these developmental processes differ in males and females? METHOD: Subjects included 1480 twin pairs from the Swedish Twin Study of Child and Adolescent Development who have been followed since 1994. Prospective, self-reported regular smoking, alcohol intoxication and illicit drug use were assessed at ages 13-14, 16-17 and 19-20 years. Structural modeling was performed with the program Mx. RESULTS: An underlying common factor accounted for the association between smoking, alcohol and illicit drug consumption for the three age groups. Common genetic and shared environmental effects showed substantial continuity. In general, as participants aged, the influence of the shared environment decreased, and genetic effects became more substance specific in their effect. CONCLUSIONS: The current report answers three important questions in the etiology of substance use. The genetic and environmental risk for substance consumption is partly mediated through a common factor and is partly substance specific. Developmentally, evidence was strongest for stability of common genetic effects, with less evidence for genetic innovation. These processes seem to be the same in males and females.

A population-based twin study of the genetic and environmental relationship of major depression, regular tobacco use and nicotine dependence.

BACKGROUND: Numerous epidemiological studies have reported a positive association between major depression (MD) and regular tobacco use (RU) or nicotine dependence (ND). However, few have used a genetically informative design to assess whether these traits share a common genetic and/or environmental liability. METHOD: We assessed MD, RU and ND in same-sex twins from the population-based Swedish Twin Registry. In males, we examined both cigarette use and snus (smokeless tobacco) use. We used structural equation modeling to examine the relationship between MD, RU, and ND given RU. RESULTS: The results suggest modest correlations between MD and RU, and between MD and ND. In males, the liability shared between MD and RU is solely genetic for both cigarettes and snus, while MD and ND share both genetic and unique environmental influences. The continuation to ND given RU differed considerably between cigarette and snus users. In females, both MD-RU and MD-ND relationships are partially attributable to genetic and unique environmental correlations. CONCLUSIONS: The relationship among MD, RU and ND is at least partially attributable to shared genetic and environmental risk factors. The genetic and environmental correlations between traits are modest. The nature of the shared liability differs by sex, and in males, by the type of tobacco product used. Differences between previous reports and results presented in the current study are suggestive of population differences in how MD and tobacco use inter-relate.

Monoamine oxidase A and childhood adversity as risk factors for conduct disorder in females.

BACKGROUND: Recent studies among males have reported a genotype-environment interaction (GxE) in which low-activity alleles at the monoamine oxidase A (MAOA) locus conferred greater sensitivity to the effects of childhood adversity on risk for conduct disorder (CD). So far, few studies of females have controlled for gene-environment correlation or used females heterozygous for this X-linked gene. METHOD: Logistic regression analysis of a sample of 721 females ages 8-17 years from the longitudinal Virginia Twin Study of Adolescent Behavioral Development (VTSABD) assessed the additive effects of MAOA genotypes on risk for CD, together with the main effect of childhood adversity and parental antisocial personality disorder (ASP), as well as the interaction of MAOA with childhood adversity on risk for CD. RESULTS: A significant main effect of genotype on risk for CD was detected, where low-activity MAOA imparted the greatest risk to CD in girls while controlling for the significant effects of maternal ASP and childhood adversity. Significant GxE with weak effect was detected when environmental exposure was untransformed, indicating a higher sensitivity to childhood adversity in the presence of the high-activity MAOA allele. The interaction was no longer statistically significant after applying a ridit transformation to reflect the sample sizes exposed at each level of childhood adversity. CONCLUSIONS: The main effect of MAOA on risk for CD in females, its absence in males and directional difference of interaction is suggestive of genotype-sex interaction. As the effect of GxE on risk for CD was weak, its inclusion is not justified.

Heritability of somatotype components from early adolescence into young adulthood: a multivariate analysis on a longitudinal twin study.

BACKGROUND: Several studies with different designs have attempted to estimate the heritability of somatotype components. However they often ignore the covariation between the three components as well as possible sex and age effects. Shared environmental factors are not always controlled for. AIM: This study explores the pattern of genetic and environmental determination of the variation in Heath-Carter somatotype components from early adolescence into young adulthood. SUBJECTS AND METHODS: Data from the Leuven Longitudinal Twin Study, a longitudinal sample of Belgian same-aged twins followed from 10 to 18 years (n = 105 pairs, equally divided over five zygosity groups), is entered into a multivariate path analysis. Thus the covariation between the somatotype components is taken into account, gender heterogeneity can be tested, common environmental influences can be distinguished from genetic effects and age effects are controlled for. RESULTS: Heritability estimates from 10 to 18 years range from 0.21 to 0.88, 0.46 to 0.76 and 0.16 to 0.73 for endomorphy, mesomorphy and ectomorphy in boys. In girls, heritability estimates range from 0.76 to 0.89, 0.36 to 0.57 and 0.57 to 0.76 for the respective somatotype components. Sex differences are significant from 14 years onwards. More than half of the variance in all somatotype components for both sexes at all time points is explained by factors the three components have in common. CONCLUSIONS: The finding of substantial genetic influence on the variability of somatotype components is further supported. The need to consider somatotype as a whole is stressed as well as the need for sex- and perhaps age-specific analyses. Further multivariate analyses are needed to confirm the present findings.

Genetic effects on the variation and covariation of attention deficit-hyperactivity disorder (ADHD) and oppositional-defiant disorder/conduct disorder (Odd/CD) symptomatologies across informant and occasion of measurement.

BACKGROUND: Previous studies have shown that the presence of conduct disorder may contribute to the persistence of attention deficit-hyperactivity disorder (ADHD) symptomatology into adolescence; however, the aetiological relationship between the two phenotypes remains undetermined. Furthermore, studies utilizing multiple informants have indicated that teacher ratings of these phenotypes are more valid than maternal reports. METHODS: The genetic structure underlying the persistence of ADHD and oppositional-defiant disorder/conduct disorder (ODD/CD) symptomatologies as rated by mothers and teachers at two occasions of measurement was investigated on a sample of 494 male and 603 female same sex adolescent twin pairs participating in the Virginia Twin Study of Adolescent Behavioral Development (VTSABD). RESULTS: Using structural modelling techniques, one common genetic factor was shown to govern the covariation between the phenotypes across informants and occasion of measurement with additional genetic factors specific to ODD/CD symptomatology and persistence of symptomatology at reassessment. Genetic structures underlying the phenotypes were, to some extent, informant dependent. CONCLUSIONS: The findings indicate that it is unlikely that the co-morbidity between ADHD and ODD/CD is due to environmental influences that are independent of ADHD. Rather it is likely to be due to a shared genetic liability either operating directly, or indirectly through gene-environment correlations or interactions. The covariation between phenotypes across informants and time is governed by a common set of genes, but it seems that ODD/CD is also influenced by additional genetic factors. Developmentally, different forms of genetic liability control ADHD in males and inattention in females.

Comparison of multiple measures of ADHD symptomatology: a multivariate genetic analysis.

The phenotypic and genetic interrelationships underlying ADHD symptomatology assessed by various instruments were examined on a sample of 735 male and 819 female same-sex twin pairs, aged 8 to 16 years, participating in the first phase of the Virginia Twin Study of Adolescent Behavioral Development (VTSABD). Multivariate analyses were applied to parental and teacher ratings from an investigator-based interview, the CAPA, and three questionnaires (the CBCL and the Rutter Parent and Teacher Scales). Results from patterns of intercorrelations and factor analyses of maternal measures suggested that at the phenotypic level, these assessed the same underlying behavioural construct, which differed from other emotional and behavioural constructs. However, genetic analyses showed that in addition to a common factor underlying the expression of ADHD as assessed across the range of measures, additional genetic factors were identified that were method- and rater-specific. The findings suggest that although the investigator-based interview and the behavioural checklists tap similar aspects of ADHD behaviour, there is additional rater-specific variance.

Parental concordance and comorbidity for psychiatric disorder and associate risks for current psychiatric symptoms and disorders in a community sample of juvenile twins.

In this report we characterize associations between parental psychiatric disorders and children's psychiatric symptoms and disorders using a population-based sample of 850 twin families. Juvenile twins are aged 8-17 years and are personally interviewed about their current history of DSM-III-R conduct, depression, oppositional-defiant, overanxious, and separation anxiety disorders using the CAPA-C. Mothers and fathers of twins are personally interviewed about their lifetime history of DSM-III-R alcoholism, antisocial personality disorder, generalized anxiety disorder, major depression, panic disorder/agoraphobia, social phobia, and simple phobia using a modified version of the SCID and the DIS. Generalized least squares and logistic regression are used to identify the juvenile symptoms and disorders that are significantly associated with parental psychiatric histories. The specificity of these associations is subsequently explored in a subset of families with maternal plus parental psychiatric histories with a prevalence > 1%. Parental depression that is not comorbid or associated with a different spousal disorder is associated with a significantly elevated level of depression and overanxious disorder symptoms and a significantly increased risk for overanxious disorder. Risks are higher for both symptomatic domains in association with maternal than paternal depression, and highest in association with maternal plus paternal depression. Risks for otherjuvenile symptoms and disorders index the comorbid and spousal histories with which parental depression is commonly associated. Paternal alcoholism that is not comorbid or associated with a maternal disorder is not significantly associated with current psychiatric symptoms or disorders in offspring. Risks for oppositional-defiant or conduct symptoms/disorders in the offspring of alcoholic parents index parental comorbidity and/or other spousal histories.

Further evidence against the environmental transmission of individual differences in neuroticism from a collaborative study of 45,850 twins and relatives on two continents.

We examine the hypothesis that environmental transmission is a significant factor in individual differences for Neuroticism among 45,850 members of extended twin kinships from Australia (N = 20,945) and the United States (N = 24,905). To this large data set we fitted a model estimating genetic and environmental components of variance and gene-environmental covariance to examine the causes of individual differences in Neuroticism. For the combined sample we reject models including environmental transmission, shared environment, and a special twin environment in favor of more parsimonious genetic models. The best-fitting model involved only modest assortative mating, nonshared environment, and both additive and nonadditive genetic components. We conclude, first, that there is no evidence for environmental transmission as a contribution to individual differences in Neuroticism in these replicated samples, drawn from different continents, and, second, that a simple genetic structure underlies familial resemblance for the personality trait of Neuroticism. It is interesting that, despite the opportunity provided by the elaborate design and extensive power of our study, the picture revealed for the causes of individual differences in Neuroticism is little more complex than that found from earlier, simpler designs applied to smaller samples. However, this simplicity could not have been confirmed without using a highly informative design and a very large sample.

Familial aggregation for conduct disorder symptomatology: the role of genes, marital discord and family adaptability.

BACKGROUND: There is extensive evidence of statistical associations between family discord/ maladaptation and antisocial behaviour in the children, but questions remain on the extent to which the psychopathological risks are genetically or environmentally mediated. METHODS: Twin pairs (N = 1,350), aged 8 to 16 years, in the general population-based Virginia Twin Study of Adolescent Behavioral Development were assessed using the Child and Adolescent Psychiatric Assessment interview administered separately to both twins and both parents. Structured interviews for parental lifetime psychiatric disorders were also administered to the mothers and fathers. Maternal reports on Olsson's Family Adaptability and Cohesiveness questionnaire and the Dyadic Adjustment Scale were used as indices of the family environment. A path analytical model based on an extended twin-family design was used to test hypotheses about parent offspring similarity for conduct disorder symptomatology. RESULTS: Family discord and maladaptation, which intercorrelated at 0.63, were associated with a roughly two-fold increase in risk for conduct disorder symptomatology. When parental conduct disorder was included in the model the environmental mediation effect for family maladaptation remained, but that for family discord was lost. CONCLUSION: It is concluded that there is true environmental mediation from family maladaptation, operating as a shared effect, which accounts for 3.5 % of the phenotypic variance. The assumptions underlying this genetic research strategy are made explicit, together with its strengths and limitations.

Genetics of peanut allergy: a twin study.

BACKGROUND: The role of genetics in the etiology of peanut allergy is unknown. For complex genetic traits, twin studies can provide information on the relative contribution of genetic factors to a disease, as the relative confounding effects of environmental factors are markedly decreased. OBJECTIVE: This study was performed to search for evidence that genetic factors influence peanut allergy by comparing the concordance rate for this allergy among monozygotic and dizygotic twins. METHODS: Twin pairs with at least one member with peanut allergy were ascertained through the Food Allergy Network by advertisements in the organization's newsletters and Web site. Individuals with peanut allergy or parental surrogates were interviewed by telephone. A full atopic history was obtained, and peanut allergy and zygosity were determined using previously validated questionnaires. Heritability of peanut allergy was determined using univariate genetic model fitting by maximum likelihood with the Mx statistical modeling software package. RESULTS: Seventy-five twin pairs were recruited. Seventeen pairs were excluded because of unconvincing peanut allergy histories (9 pairs, including 4 of uncertain zygosity) or because one twin had reportedly never ingested peanut (8 pairs). The median age of the 58 remaining twin pairs was 5 years (range 1 to 58 years). Seventy individuals had peanut allergy. In addition to convincing histories of peanut allergy, 52 (74%) had been tested (skin prick testing with or without radioallergosorbent assay) and all had positive reactions to peanut. Twenty-nine of the 70 had experienced >1 reaction to peanut; 29 of 70 had multisystem reactions. Among the monozygotic pairs (n = 14), 9 were concordant for peanut allergy (pairwise concordance, 64.3%) and among dizygotic pairs (n = 44), 3 were concordant for peanut allergy (pairwise concordance, 6.8%; chi(2) = 21.38, P <.0001). Heritability of peanut allergy was estimated at 81. 6% (95% confidence interval 41.6% to 99.7%) with model fitting using a population prevalence of peanut allergy of 0.4%. CONCLUSIONS: The significantly higher concordance rate of peanut allergy among monozygotic twins suggests strongly that there is a significant genetic influence on peanut allergy.

Genetic variance of adolescent growth in stature.

The aim of this study is to quantify the genetic and environmental variation in biological parameters of the adolescent growth in stature in both sexes, using structural equation models. Standing height was measured in 99 twin pairs from the Leuven Longitudinal Twin Study. Subjects were seen at semi-annual intervals between 10 and 16 years and at 18 years. Preece-Baines model I was fitted to the individual data and biologically meaningful parameters were derived. Path models were fitted to these parameters and a gender heterogeneity analysis was performed. A model including additive genetic and specific environmental factors (AE-model), allowing for a difference in total variance or in genetic/environmental variance components in males and females best explains most of the growth characteristics. For the timing and velocity of the adolescent growth spurt, no gender heterogeneity was observed, and the genetic (0.89 to 0.93) and specific environmental (0.07 to 0.11) contributions were equal in both sexes. For stature at take-off, stature at peak height velocity and for adult stature, gender heterogeneity was observed and different models appeared to result in the best fit for boys and girls. For height at PHV and adult stature, the significant contribution of a common environmental (0.39 to 0.56) factor in boys was noteworthy. For percentage of adult stature and distances between relevant time points of the growth curve, a non-scalar effect was observed, indicating that different genes affect these characteristics in boys and girls. It is concluded that most characteristics of the growth spurt in stature are under strong genetic control. Gender heterogeneity is present for stature and for a number of derived growth characteristics.

Predictive power of individual genetic and environmental factor scores.

This study explores the use of an individual's genetic (IGFS) and environmental factor score (IEFS), constructed using genetic model fitting of a multivariate strength phenotype. Maximal isometric and dynamic strength measures, one maximal repetition load (1RM) and muscle cross-sectional area (MCSA) were measured in 25 monozygotic and 16 dizygotic twin pairs. The use of IGFS and IEFS in predicting the sensitivity to environmental stress was evaluated by the association of the scores with strength training gains after a 10-week high resistance strength training programme. Results show a high contribution of genetic factors to the covariation between maximal strength and muscle cross-sectional area (84-97%) at pre-training evaluation. Individual factor scores explained the largest part of the variation in IRM and other strength measures at pre-training and post-training evaluation respectively. Genes that are switched on due to training stress (gene-environment interaction) could explain the decrease in explained variation over time. A negative correlation was found between IGFS and strength training gains (-0.24 to -0.51, P < 0.05); individuals with a high IGFS tend to gain less strength than individuals with low IGFS. Individual environmental factor scores have lower differential power. The predictive value of the IGFS has potential utility in identifying an individual's susceptibility to environmental stress in a variety of multifactorial characteristics, eg diseases and impairments, and for selection of sib pairs for QTL analyses.

Frequency of church attendance in Australia and the United States: models of family resemblance.

Data on frequency of church attendance have been obtained from separate cohorts of twins and their families from the USA and Australia (29,063 and 20,714 individuals from 5670 and 5615 families, respectively). The United States sample displayed considerably higher frequency of attendance at church services. Sources of family resemblance for this trait also differed between the Australian and US data, but both indicated significant additive genetic and shared environment effects on church attendance, with minor contributions from twin environment, assortative mating and parent-offspring environmental transmission. Principal differences between the populations were in greater maternal environmental effects in the US sample, as opposed to paternal effects in the Australian sample, and smaller shared environment effects observed for both women and men in the US cohort.

Adolescent religiousness and its influence on substance use: preliminary findings from the Mid-Atlantic School Age Twin Study.

Research has consistently shown that religiousness is associated with lower levels of alcohol and drug use, but little is known about the nature of adolescent religiousness or the mechanisms through which it influences problem behavior in this age group. This paper presents preliminary results from the Mid-Atlantic School Age Twin Study, a prospective, population-based study of 6-18-year-old twins and their mothers. Factor analysis of a scale developed to characterize adolescent religiousness, the Religious Attitudes and Practices Inventory (RAPI), revealed three factors: theism, religious/spiritual practices, and peer religiousness. Twin correlations and univariate behavior-genetic models for these factors and a measure of belief that drug use is sinful reveal in 357 twin pairs that common environmental factors significantly influence these traits, but a minor influence of genetic factors could not be discounted. Correlations between the multiple factors of adolescent religiousness and substance use, comorbid problem behavior, mood disorders, and selected risk factors for substance involvement are also presented. Structural equation modeling illustrates that specific religious beliefs about the sinfulness of drugs and level of peer religiousness mediate the relationship between theistic beliefs and religious/spiritual practices on substance use. Limitations and future analyses are discussed.

Religious attendance and frequency of alcohol use: same genes or same environments: a bivariate extended twin kinship model.

Religious attendance has been shown to correlate negatively with alcohol use. We investigated whether this relationship is driven by genetic or environmental factors. Data on frequency of church attendance and frequency of alcohol use were obtained from twins and their families in the Virginia 30,000 study. A comprehensive bivariate model of family resemblance was fitted to the data using Mx. This model is described in detail. Results indicate that genetic factors primarily account for the relationship between alcohol and church attendance in males, whilst shared environmental factors, including cultural transmission and genotype-environment covariance, are stronger determinants of this association in females.

Tuberculosis I: a conceptual frame for the immunopathology of the disease.

An analysis of the cellular and humoral immune responses after bacille Calmette-Guerin (BCG) vaccination and during tuberculosis treatment favors the hypothesis of an immune defence developed in four overlapping successive stages. The initial immune response is innate. The following two intermingle innate and specific responses against low molecular weight oligopeptidic and nonpeptidic antigens, as muramyldipeptide and trehalose dimycolate, and large molecular weight nonpeptidic antigens such as lipoarabinomannan. The ultimate specific response is directed against protein antigens as Antigen 60. BCG and primary tuberculosis (TB) infections induce cellular and humoral immune responses essentially against oligopeptidic and small and large molecular weight nonpeptidic antigens. Immune responses against non-peptidic substances contribute to the immunoprotection of the infected person who develops a primary infection. Some infected people allow the expression of the immunosuppressive activity of the pathogen. This results in the synthesis of interleukin-10 (IL-10), which suppresses the formation of interferon-gamma (INF-gamma) and IL-2, and of IL-6, which suppresses T-cell responses. These patients have a skewed immune response against non-peptidic antigens and present with symptoms. They will not recover unless responses directed against proteinic antigens occur, which restore INF-gamma and IL-2 production. The formation of immumoglobulin-G (IgG)-type antibodies and of a cellular immunity against mycobacterial peptidic antigens is essential for a good protection against a post-primary infection.