EPHA4 Genetic Variant in a Patient with Epilepsy, Ophthalmological Anomalies, and Neurodevelopmental Delay.

We present the findings of a Whole Exome Sequencing in a 2-year-old boy, conceived via In Vitro Fertilization with donor sperm, who suffers from an undiagnosed neurological syndrome. The following heterozygous variant in the EPHA4 gene was identified and classified as likely pathogenic: c.1655_1656, p.(Ser552CysfsTer23). Subsequent segregation analysis showed that the variant was not inherited from the mother and the sperm donor is not accessible for genetic testing. The presented results can further expand upon the genetic variants considered when diagnosing complex neurological syndromes and shows the importance of access to biological samples from donor banks in genetically ambiguous cases.

Novel Mutation in the COL11A1 Gene Causing Marshall-Stickler Syndrome in Three Generations of a Bulgarian Family.

Here we report the first familial case spread through at least three generations, genetically verified cases of Marshall-Stickler syndrome in Bulgaria. The proband, a 2-year-old girl, has craniofacial dysplasia, ocular hypertelorism, small saddle nose with a flat bridge and midface hypoplasia. The pedigree of the proband's family showed that her father has the same clinical manifestations of the disease. In addition, her father presented with a tall, thin stature and mild hearing loss, manifested with aging. The same dysmorphological symptoms were presented by the paternal grandfather. Both patients, the 2-year-old girl and her father, have been diagnosed to carry Marshall-Stickler syndrome. The COL2A1 gene tested negative in the family. Based on the higher percentage of mutations in the COL2A1 gene, we analyzed this gene as the first target in the family. The COL2A1 gene tested negative, and we sequenced the gene further. A novel splice site mutation c.3474+1G>A was found in intron 44. This variant is related to the clinical presentation in the patient and her father. The c.3474+1G>A mutation results in altered splicing affects at the donor splice site of intron 44, which most probably gives a nonfunctional protein. The variant affects the major triple-helical domain that represents a mutation hot-spot for the gene.

Molecular genetic diagnostics of tuberous sclerosis complex in Bulgaria: six novel mutations in the TSC1 and TSC2 genes.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by the development of hamartomas localized in various tissues which can occur in the skin, brain, kidney and other organs. TSC is caused by mutations in the TSC1 and TSC2 genes. Here we report the results from the first molecular testing of 16 Bulgarian patients and one Romanian patient in whom we found six novel mutations: four in the TSC22 gene, of which one is nonsense, two frame shift and one large deletion of 16 exons; and two in the TSC1 gene, one nonsense and other frame shift. In addition, we detected 10 previously reported mutations; some of which are described only once in the literature. Our data is similar to the previous studies with exception of the larger number of TSC1 mutations than that reported in the literature data. In total, 40% (4/10) of the mutation in the TSC2 gene are located in the GTPase-activating protein domain, while 50% (3/6) are in the TSC1 gene and clustered in exon 15. All the cases represent the typical clinical symptoms and meet the clinical criteria for TSC diagnosis. In 35% of our cases the family history was positive. Our results add novel findings in the genetic heterogeneity and pathogenesis of TSC. The genetic heterogeneity might correlate to the clinical variability among the TSC-affected families, which makes the genetic counselling a real challenge.

Method to characterize inorganic particulates in lung tissue biopsies using field emission scanning electron microscopy.

Humans accumulate large numbers of inorganic particles in their lungs over a lifetime. Whether this causes or contributes to debilitating disease over a normal lifespan depends on the type and concentration of the particles. We developed and tested a protocol for in situ characterization of the types and distribution of inorganic particles in biopsied lung tissue from three human groups using field emission scanning electron microscopy (FE-SEM) combined with energy dispersive spectroscopy (EDS). Many distinct particle types were recognized among the 13 000 particles analyzed. Silica, feldspars, clays, titanium dioxides, iron oxides and phosphates were the most common constituents in all samples. Particles were classified into three general groups: endogenous, which form naturally in the body; exogenic particles, natural earth materials; and anthropogenic particles, attributed to industrial sources. These in situ results were compared with those using conventional sodium hypochlorite tissue digestion and particle filtration. With the exception of clays and phosphates, the relative abundances of most common particle types were similar in both approaches. Nonetheless, the digestion/filtration method was determined to alter the texture and relative abundances of some particle types. SEM/EDS analysis of digestion filters could be automated in contrast to the more time intensive in situ analyses.

BARTH SYNDROME IN MALE AND FEMALE SIBLINGS CAUSED BY A NOVEL MUTATION IN THE TAZ GENE.

Barth syndrome (BTHS) is an X-linked recessive disease caused by mutations in tafazzin gene (TAZ) which lead to cardiolipin deficiency and mitochondrial dysfunction. Male patients have variable clinical findings, including cardiomyopathy, skeletal myopathy, prepubertal short stature, neutropenia and 3-methylglutaconic aciduria. Female carriers are usually asymptomatic. We report a novel TAZ gene mutation in male and female siblings with left ventricular noncompaction and hypotonia. Additionally, the brother presented an intermittent neutropenia and increased urinary levels of 3-methylglutaconic and 3-methylglutaric acid. The molecular genetic testing showed that both siblings carry the mutation: c.253insC, p.(Arg85Profs*54) in exon 3 of the TAZ gene. This article presents the first case of BTHS in a heterozygous female patient with normal karyotype.

[Pregnant women's attitudes towards the acceptable age limits for conceiving and giving birth to a child].

AIM: To assess whether there are socially determined permissible and desirable age limits for conceiving and childbirth among pregnant women in Bulgaria and their relation to age, general and obstetrical medical history, method of conception, level of education and whether pregnancy has been postponed or not. MATERIALS AND METHODS: 388 patients from the Fetal Medicine Clinic of the State University Hospital "Maichin Dom" in Sofia were provided with anonymous questionnaires, containing 38 questions. Two of the questions were essensial: 1) "What is the maximal permissible age for a woman to become pregnant and give birth to a child?". 2) "What is the maximal desirable age for a woman to become pregnant and deliver the planned numberof children?". The questionnaire contained also 23 questions related to the demographic characteristics of the participants and to their general and obstetric medical history. Data were processed with SPSS 13.0 statistical package. Descriptive and comparative analysis was performed after grouping according to one or mare chracteristics. P values < 0.05 were considered statistically significant. RESULTS: 54.2% (208/388) of the respondents determined a limit of the maximal permissible age for woman to conceive and give birth to a child. 53.4% (111/208) of them set the age limit of 40 years (28.9% of all patients). 63.6% (245/388) of the interrogated set a desirable age limit for conception and giving birth. Among then 82.9% (203/245) have set the limit at 40 years. The factors that influenced significantly the attitude towards the permissible age forconception/giving birth were the mode of conception, age and the level of education. Patients who had conceived spontaneously and had higher educational level were more confident when assessing the permissible age for conception/giving birth. Patients who had conceived by IVF/ICSI were significantly less confident answering the questions about age limits. The understanding for the permissible age for conception was not influenced by past obstetric history, deliberate postponemend of reproductive plans and the presence of chronic medical disorders. The understanding that pregnancy is always permissible (irrespective of age) was not influenced significantly by any of the factors. The understanding about the desirable age for conceiving/giving birth was influenced significantly only by the educational level--patients with higher degree of education were more confident in setting a desirable age limit.

First Bulgarian case of citrin deficiency caused by one novel and one recurrent mutation in the SLC25A13 gene.

Citrin deficiency is an autosomal recessive disorder caused by mutations in the SLC25A13 gene and has three phenotypes: neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) in newborns, failure to thrive and dyslipidemia caused by citrin deficiency (FTTDCD) in older children, and recurrent hyperammonemia with neuropsychiatric symptoms in citrullinemia type II (CTLN2) in adults. NICCD presents in the first few weeks of life with cholestatic hepatitis syndrome, multiple aminoacidemia and hypergalactosemia. To date almost all reported patients were from East Asia and only few cases from Caucasian origin have been described. We report the first Bulgarian case of NICCD. Mutation screening of the SLC25A13 gene revealed the compound heterozygous mutations c.1081C>T (p.R361*) and c.74C>A (p. A25E) which confirmed the diagnosis of NICCD. The nonsense mutation c.1081C>T (p.R361*) is novel.

APC promoter 1B deletion in familial polyposis--implications for mutation-negative families.

Over 1500 adenomatous polyposis coli (APC) gene mutations have already been identified as causative of familial adenomatous polyposis (FAP). However, routine genetic testing fails to detect mutations in about 10% of classic FAP cases. Recently, it has been shown that a proportion of mutation-negative FAP cases bear molecular changes in deep intronic and regulatory sequences. In this study, we used direct sequencing, followed by multiplex ligation-dependent probe amplification (MLPA) of genomic DNA from family members, affected by classic FAP. We first reported the family as mutation negative. With the launch of a new version of MLPA kit, we retested the family and a novel full deletion of promoter 1B was detected. The exact breakpoints of the deletion were determined by array comparative genomic hybridization (CGH) and long range polymerase chain reaction (PCR), followed by direct sequencing. The total APC expression levels were investigated by quantitative polymerase chain reaction (qPCR) assay and allele-specific expression (ASE) analysis. The APC gene expression was highly reduced, which indicates causative relationship. We suggest that there is a significant possibility that APC promoter 1B mutations could be found in mutation-negative FAP patients. In the light of our findings it seems reasonable to consider targeted genetic re-analysis of APC promoter 1B region in a larger cohort of unsolved cases.

A family with fragile X syndrome, Duchenne muscular dystrophy and ichthyosis transmitted by an asymptomatic carrier.

The human X chromosome carries regions prone to genomic instability: deletions in the Xp22.31 region, involving the steroid sulfatase gene (STS) cause X-linked ichthyosis; rearrangements in the Xp21.2 region are associated with Duchenne or Becker muscular dystrophies (DMD or BMD); and the Xq27.3 unstable region, containing the (CGG)n repeat expansion in the FMR1 gene is associated with fragile X syndrome. We report on a family with two affected boys, the elder diagnosed with fragile X syndrome, the younger with DMD, and both suffering from severe ichthyosis. The family was analyzed by polymerase chain reaction, multiplex ligation-dependent probe amplification and haplotype analysis. The mother proved to be an asymptomatic carrier of all three non-contiguous mutation events, involving the STS gene, the DMD gene and a FMR1 expansion. To the best of our knowledge, this is the first description of an asymptomatic carrier of three different X-linked disorders, involving severe genetic rearrangements on both long and short arms of the X chromosomes. The boy with fragile X syndrome has inherited a triple recombinant maternal X chromosome, this way inheriting the FMR1 expansion and ichthyosis, originating most probably from different maternal Xes and excluding the DMD gene deletion. The transmission of these extremely defective maternal chromosomes to the next generation involved several recombinations.

[Mode of conception, acompanying medical disorders and complications in the second half of pregnancy in women over the age of 35].

AIM: To assess the impact of maternal age on the mode of conception, the incidence of accompanying medical disorders and past surgical procedures (gynecological and non-gynecological) and the complications in the second half of pregnancy (preeclampsia, placenta praevia, placental abruption, preterm delivery) in women ≥ 35 years, followed prospectively. MATERIALS AND METHODS: Between 02/2012 - 02/2014 495 pregnant women of ≥ 12 weeks of gestation were enrolled in the study. The patients were admitted for different indications at the Fetal Medicine Clinic of the State University Hospital "Maichin Dom". They were divided in 3 age groups according to age: ≤ 34, 35-39 and ≥ 40 years. The information about pregnancy course and outcome was retrieved from the hospital records or obtained from the patents themselves by phone interviews. The following complications in the second half of pregnancy were analyzed: preeclampsia, placenta praevia, placental abruption, preterm delivery. The data were processed with SPSS 13.0. statistical package. Descriptive and comparative analysis was performed after grouping according to one or more characteristics; p values < 0.05 were considered as evidence of statistical significance for tested effects. RESULTS: The number of patients ≤ 34 years of age was 131/495 (26.5%), between 35-39 years--54/495 (51,.%) and >≥40 years --10/495 (22,.%). Conception by ART was significantly more frequent in women aged >3 5. Pregnancy occurred afterA RTi n 1,.% (2/131) of the women <3 4, in 8,.% (22/254) of those between 35-39 and in 10,.% (12/110) of those >≥ 0 years of age (p= O 0.08). The incidence of accompanying medical disorders (intemrnl, tumors, of the female genital system) was significantly higher in women of more advanced age (p< O 0.01). It was 36,.% (48/131) in those <3 4, 53,1% (135/254) --n the ones between 35-39 and 68,.% (75/110) --mong those >≥ 0 years of age. The increased incidence was mainly due to more frequent intemrnl (p= 0 ,.218) and female reproductive system (p=0,0027) disorders. The incidence of past surgical procedures was increased significantly with advancing maternal age; this was attributed mainly to non-gynecological surgical procedures (p= O 0.04). Among women <3 4 years 41,.% (54/131) reported past surgery, while in the age groups between 35-39 and >≥ 0 years the figures were 57,.% (146/254) and 59, 1% (65/110) respectively .The increase of maternal age was related to significantly more frequent complications in the second half of pregnancy --reeclampsia, placenta praevia, placental abruption and preterm delivery. The incidence of preeclampsia increased from 1,.3% (2/131) in the age group <3 4, to 3,.3% (10/254) for those aged 35-39 and to 7,.7% (8/110) --or the ones _≥ 0 (p= O 0.5). The combined incidence of placenta praevia and placental abruption was also significantly higher in women of more advanced age (p= 0 ,.056). In the age group <3 4 no such cases were registered while in women aged 35-39 the incidence of these complications was 3, 14% (8/254) and for the age group >≥ 0 it was 8,.8% (9/110). The combined incidence of placenta previa and placental abruption was considered because of the small number of cases. The complications cited above were significantly more frequent in women with accompanying medical disorders (p = 0,001). The incidence of preterm deliveries increased significantly with maternal age --rom 10,.% (14/131) for women <3 4 to 25,.% (52/208) --or those between 35-39 and 21,.% (20/93) --or those _≥ 0 years of age (p= 0 ,.13). The combined preterm delivery rate was considered in the study (spontaneous and induced). CONCLUSION: In our study maternal age >≥ 5 years was related to significantly more frequent conception by ART history of accompanying medical disorders, past surgery (non-gynecological) and complications in the second half of pregnancy (preeclampsia, placenta praevia, placental abruption and preterm delivery).

[Pregnancy outcome in women over the age of 35].

AIM: To assess pregnancy outcome in women aged > or =35, followed prospectively, and the relation between maternal age and the incidence of abortions after 12 gw (spontaneous and medical), preterm delivery, mode of delivery and congenital anomalies. MATERIALS AND METHODS: 495 women from the Fetal Medicine Clinic of the State University Hospital "Maichin Dom" in Sofia were enrolled in the study between 02/2012 and 02/2014 with gestational age > or =12 completed weeks. The patients were devided in 3 groups according to age-- < or =34, between 35 and 39 and > or = 40 years of age. Pregnancy outcome was veirified from hospital records and phone intenrviews with the patients themselves. Data were processed with SPSS 13.0 statistical package. Descriptive and comparative analysis was performed after grouping according to one or more characteristics; p values <0.05 were considered as evidence of statistical significance for tested effects. RESULTS: 131/495 (26.5%) of the patients were < or =34 years of age, 254/495 (51.3%) were between 35 and 39 and 110/495 (22.2%) were > or =40 years of age. Maternal age > or =35 was associated with statistically significant increase of the total late abortion rate (spontaneous and medical abortions)--from 6.9% for those < or =34 yars of age to 11.3%--for the ones between 35-39 and 11.4%--for the ones > or =40 years. There was also statistically significant increase in the incidence of late medical abortions in the group > or =40 years of age (p=0.011). It was 2/124 (1.6%) for the group aged < or =34, 7/230 (3%)--in the group aged 35-39 and 9/100 (9.0%)--in the group > or =40 years of age. The difference in late spontaneous abortions rate was not statistically significant among the groups. There was statistically significant increase in the incidence of preterm deliveries (spontaneous and induced)--14/131 (10.7%) in the group aged < or =34, 52/208 (25.0%)--in the group between 35-39 and 20/93 (21.5%)--in the group > or =40 years of age (p=0.013). There was also a significant increase in Cesarean section rate with age--from 44/131 (33.6%) in the group < or =34, to 139/254 (54.7%)--in the group between 35-39, and 69/110 (62.7%)--in the group > or =40 years (p=0.0001). There is a tendency for increased operative vaginal delivery rate with age; however the difference is not statistically significant, probably due to the small number of cases (p=O. 113). There was also statistically significant increase in the proportion of newborns with congenital anomalies in women > or =40 years of age (p=0.005)--from 1/131 (0.8%) in patients < or =34, to 2/254 (1.0%) for those between 35 and 39, and 6/110 (5.5%)--for those > or =40 years. Part of the congenital anomalies was prenatally diagnosed chromosomal defects without termination of pregnancy CONCLUSIONS: Maternal age > or =35 years is associated with statistically significant increase in late medical abortions, preterm delivery and Cesarean section rate and congenital fetal anomalies.

Association between loss of dp140 and cognitive impairment in duchenne and becker dystrophies.

The presence of variable degrees of non progressive cognitive impairment is recognized as a clinical feature of patients with Duchenne and Becker muscular dystrophies (DMD and BMD), but its pathogenesis still remains a matter of debate. A number of findings have proved that rearrangements located in the second part of the dystrophin ( DMD ) gene seem to be preferentially associated with cognitive impairment. Dp140 is a distal dystrophin isoform, mainly expressed during fetal brain development, whose role for neuropsychological functioning was suggested. The aims of the current study were to explore the possible association between cognitive impairment and DNA mutations affecting the regulatory regions of Dp140, as well as to compare the neuropsychological functioning of patients affected with DMD and Intermediate muscular dystrophy (IMD) with those affected by Becker muscular dystrophy (BMD). Fiftythree patients genetically diagnosed with DMD, IMD and BMD, subdivided according to sites of mutations along the DMD gene, underwent a neuropsychological assessment, evaluating their general cognitive abilities, verbal memory, attention and executive functions. Twenty patients with mutations, terminating in exon 44 or starting at exon 45 were tested by polymerase chain reaction (PCR) amplification of microsatellites STR44, SK12, SK21 and P20 DXS269, in order to evaluate the integrity of the Dp140 promoter region. According to our statistical results, there was not a significant difference in terms of general intelligence between the allelic forms of the disease, a higher frequency of mental retardation was observed in DMD patients. The patients with BMD had better results on tests, measuring long-term verbal learning memory and executive functions. We found that patients lacking Dp140 performed more poorly on all neuropsychological tests compared to those with preserved Dp140. Overall, our findings suggest that the loss of Dp140 is associated with a higher risk of intellectual impairment among patients with dystrophinopathies and highlights the possible role of this distal isoform in normal cognitive development.

Targeted silencing of DNA-specific B cells combined with partial plasma cell depletion displays additive effects on delaying disease onset in lupus-prone mice.

Targeting autoreactive B lymphocytes at any stage of their differentiation could yield viable therapeutic strategies for treating autoimmunity. All currently used drugs, including the most recently introduced biological agents, lack target specificity. Selective silencing of double-stranded DNA-specific B cells in animals with spontaneous lupus has been achieved previously by the administration of a chimeric antibody molecule that cross-links their DNA-reactive B cell immunoglobulin receptors with inhibitory FcγIIb (CD32) receptors. However, long-lived plasmacytes are resistant to this chimeric antibody as well as to all conventional treatments. Bortezomib (a proteasome inhibitor) depletes most plasma cells and has been shown recently to suppress disease activity in lupus mice. We hypothesized that the co-administration of non-toxic doses of bortezomib, that partially purge long-lived plasma cells, together with an agent that selectively silences DNA-specific B cells, should have additive effects in an autoantibody-mediated disease. Indeed, our data show that the simultaneous treatment of lupus-prone MRL/lpr mice with suboptimal doses of bortezomib plus the chimeric antibody resulted in the prevention or the delayed appearance of the disease manifestations as well as in a prolonged survival. The effect of the combination therapy was significantly stronger than that of the respective monotherapies and was comparable to that observed after cyclophosphamide administration.

Vitamin D status in Bulgaria--winter data.

UNLABELLED: We assume that 25(OH)D level >50 nmol/l is necessary for adequate parathyroid hormone (PTH) suppression in our population. The epidemiology of vitamin D status in Bulgarian population shows deficiency in 21.3 %, insufficiency in 54.5 % and sufficiency in 24.2 %. The mean level of 25(ОН)D for the Bulgarian population is 38.75 nmol/l (95 % CI, 38.00-39.49). PURPOSE: The aim of the present study was to investigate the vitamin D levels in Bulgaria and the prevalence of vitamin D deficiency depending on gender and age, as well as to define population-specific 25(OH)D sufficiency thresholds through the relationship with PTH. MATERIAL AND METHOD: This cross-sectional study was conducted in January-February 2012 and included 2,032 subjects in 12 regions-1,076 women (53 %) and 956 men (47 %), mean age 49.30 ± 14.75 years (20-80 years), divided into three age groups: young (20-44 years, n = 894), middle-aged (45-59 years, n = 534), and elderly (≥60 years, n = 604). 25(OH)D and PTH were measured in all subjects. RESULTS: The mean level of 25(ОН)D was 38.75 nmol/l (95 % CI, 38.00-39.49). The men had significantly higher 25(ОН)D levels in comparison to women (41.51 nmol/l (95 % CI, 40.45-42.56) vs.36.29 nmol/l (95 % CI, 35.27-37.32), p < 0.05). We did not find significant differences in the 25(ОН)D levels between the three age groups. The prevalence of vitamin D deficiency was 21.3 %; insufficiency, 54.5 %; and sufficiency, 24.2 %. Deficiency was more prevalent in women (26.9 %) than in men (15.1 %), p < 0.001. PTH started to rise over the upper limit of the reference range at mean 25(OH)D 50 nmol/l. We assume that levels over 50 nmol/l are necessary for adequate PTH suppression. CONCLUSIONS: The status of vitamin D in our country is worrisome, and it is largely underestimated. The defining of a vitamin D sufficiency levels may help the devising of adequate strategies for prevention and treatment in clinical practice.

Analysis of the genes encoding neuroligins NLGN3 and NLGN4 in Bulgarian patients with autism.

Many studies have supported a genetic aetiology for autism. Neuroligins are postsynaptically located cell-adhesion molecules. Mutations in two X-linked neuroligin genes, NLGN3 and NLGN4, have been implicated in pathogenesis of autism. In order to confirm these causative mutations in our autistic population and to determine their frequency we screened 20 individuals affected with autism. We identified one patient with a point mutation in NLGN4 gene that substituted a Met for Thr 787 - c.2360C > T, p.(Thr787Met) and three patients with identical polymorphisms in the same gene: c.933C > T, p.(Thr311Thr) in combination with c.[1777C > T+1779C > G, p.(Leu593Leu)]. All patients tested for NLGN3 mutations were negative. These results indicate that mutations in these genes are responsible for at most a small fraction of autism cases.

Morphological characteristics of the canine and feline stomach mucosa.

The stomach mucosa structure in animals belonging to Order Carnivora indicates some specific characteristics in comparison with the other mammals. Between the bases of the mucosal glands and the lamina muscularis mucosae there is an additional plate which most of the morphologists have defined as lamina subglandularis. In currently used Nomina histologica this layer is indicated as stratum compactum in carnivorous stomach mucosa. The investigation aims were to study and compare canine and feline stomach tunica mucosa characteristics as well as to measure the thickness of stratum compactum and to specify some of the certain collagen types and fibronectin compounds. Conventional and differential histological and ultrastructural methods and immuno-histochemical approaches for investigation of the canine and feline stomach samples were used. The specific organization of the carnivorous stomach wall arrangement was established. In the structure of the canine stomach mucosa, no evidence of stratum compactum was observed. The presence of stratum compactum in feline stomach mucosa was ascertained and measured. Using an immunohistochemical method very high expression of collagen type IV and fibronectin, moderate positive reaction of collagen type III, and a comparatively weakest expression of collagen types I and V in the structure of stratum compactum from cat stomach mucosa was shown. The obtained results clarify the characteristics of the stomach mucosa morphology and could be used as a basis for distinguishing the stomach wall structure of the animal species belonging to Canidae and Felidae families although they are both carnivores.

Target silencing of disease-associated B-lymphocytes by chimeric molecules in SCID model of pristane-induced autoimmunity.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the generation of autoantibodies against a diverse array of self-antigens. The B cells producing immunoglobulin G (IgG) antibodies to double-stranded DNA appear to play a main role in the disease progression. Their specific elimination is a reasonable mechanism for effective therapy of SLE. The presently used approaches for silencing autoreactive disease-associated B cells are nonspecific and more precise therapies are needed. We have previously constructed a chimeric protein molecule consisting of several DNA-mimotope peptides coupled to a rat monoclonal anti-mouse CD32 (FcγRIIb) antibody. The mineral oil pristane induces a lupus-like syndrome in non-autoimmune mice leading to the development of glomerulonephritis and lupus-associated autoantibodies. In the present paper, using a pristane-induced autoimmune model in SCID mice, we analyzed the ability of the chimeric antibody to suppress selectively the autoreactive B lymphocytes by cross-linking B-cell surface immunoglobulin receptors with the inhibitory IgG FcγRIIb receptors. Treatment with DNA-like chimeric molecules inhibited B- and T-cell proliferation, restricted the number of anti-DNA antibody-producing cells and suppressed the generation of IgG anti-DNA antibodies. In contrast, phosphate buffered saline (PBS)-injected control mice experienced an increase of disease-associated antibody levels and developed glomerulonephritis similar to pristane-treated donor Balb/c mice.