Clinical Outcomes of Thermal Ablation Re-Treatment of Benign Thyroid Nodules: A Multicenter Study from the Italian Minimally Invasive Treatments of the Thyroid Group.

Background: Thermal ablation (TA) is an established therapeutic option alternative to surgery in patients with solid benign thyroid nodules causing local symptoms. However, a variable part of thyroid nodules remain viable after these nonsurgical treatments, and as many as 15% of nodules treated with TA may require a second treatment over time. This study aimed to evaluate the outcomes of TA re-treatment on symptomatic benign thyroid nodules where the volume decreased by <50% after the first procedure ( = technique inefficacy). Methods: We performed a multicenter retrospective cohort study including patients who underwent re-treatment with TA for benign thyroid nodules, whose volume decreased by <50% after initial treatment. The primary aim was to evaluate volume and volume reduction ratio (VRR) over time and compare the 6- and 12-month VRR after first versus second treatment. The secondary aim was to identify protective or risk factors for technique inefficacy, regrowth, and further treatments, expressed as adjusted hazard ratios (HRs) and confidence interval [CI], after adjustment for sex, age, nodule volume, structure and function, nodule regrowth or symptom relapse, technique used and if the same technique was used for the first and second TA and time between them. Results: We included 135 patients. Re-treatment led to VRR of 50% and 52.2% after 6 and 12 months. VRR after re-treatment was greater than after first treatment in small and medium size nodules (<30 mL), while there were no differences for large nodules (>30 mL). After re-treatment technique inefficacy rate was 51.9%, regrowth rate was 12.6%, and further treatment rate was 15.6%. Radiofrequency ablation (RFA) was protective toward technique inefficacy (HR = 0.40 [CI 0.24-0.65]) and need of further treatments (HR = 0.30 [CI 0.12-0.76]). Large nodule volume (>30 mL) was associated with increased risk of re-treatment (HR = 4.52 [CI 1.38-14.82]). Conclusions: This is the first study evaluating the outcomes of re-treatment on symptomatic benign thyroid nodules with a VRR <50% after the initial TA treatment. Best results were seen in small and medium nodules (<30 mL) and after RFA. Prospective confirmatory studies are needed.

2022 Expert consensus on the use of laser ablation for papillary thyroid microcarcinoma.

OBJECTIVE: With the aim of standardizing and improving the use of ultrasound-guided PLA on PTMC, a panel of experts from China and Italy, jointly issued this expert consensus on the clinical use of PLA for low-risk PTMC. METHODS: This expert consensus was developed by Chinese and Italian experts who have specific competence and expertise in this area. An evidence-based approach combining the knowledge and practical experience of the panelists was utilized. RESULTS: Twenty-six expert consensus recommendations were developed, spanning topics including the indications and contraindications of PLA for PTMC, physician training, preoperative preparation of patients, intraoperative technical procedures, possible complications, efficacy assessment, follow-up strategy, the approach to new PTMC and metastatic lymph nodes after treatment, thyroid-stimulating hormone inhibition therapy, and quality control of the entire procedure. CONCLUSION: We summarized practical recommendations about standardized and improved PLA treatment for PTMC.

Ultrasound-guided laser ablation of very large benign thyroid nodules: 4-year, retrospective follow-up in 24 patients.

BACKGROUND: Percutaneous, ultrasound-guided laser ablation is a proven management approach for the treatment of Benign Thyroid Nodules (BTN), but only sporadic cases of treatment of large-volume nodules with laser ablation have been reported. The aim of this study was to evaluate the efficacy and safety of laser ablation in the treatment of very large (> 100 mL) thyroid nodules. METHODS: Between 2009 and 2016, 24 patients with very large, BTN received 2-3 sessions of laser ablation over the course of 12 months. Nodule volume was measured before treatment, and at 1 and 4 years. RESULTS: Prior to treatment, median nodule volume was 138 mL (range: 102-289 mL). At 1 year, technique efficacy was achieved in 75% of patients, with median nodule volume significantly reduced to 26 mL (range: 15-31 mL, p < 0.001 vs pretreatment). Volume reduction ratio (VRR) at 1 year was 81%. At 4-year follow-up, median nodule volume was 27 mL (range: 15-33 mL, p < 0.001 vs pretreatment), with a VRR of 80%. Two patients had nodule regrowth > 50% and went to surgery - one patient after 1 year and the other after 3 years. Treatment was well tolerated; there were no major complications, although transient fever occurred in 12% (3/24) of patients and mild-to-moderate pain was experienced by 8% (2/24) of patients. CONCLUSIONS: In this patient series, percutaneous, ultrasound-guided laser ablation of very large thyroid modules provided long-term benefits and the treatment was well tolerated.

Image-guided thermal ablation in autonomously functioning thyroid nodules. A retrospective multicenter three-year follow-up study from the Italian Minimally Invasive Treatment of the Thyroid (MITT) Group.

OBJECTIVES: To report the results of a multicenter retrospective evaluation of the clinical outcomes of thermal ablation (TA) in a large series of autonomously functioning thyroid nodules (AFTN) with a follow-up protracted up to 3 years. METHODS: Patients treated with single TA for an AFTN in Italy were included. Changes in nodule volume, TSH values, and ongoing anti-thyroid therapy were assessed at the 2-, 6-, 12-, 24-, and 36-month follow-up controls. Complications and need of any additional therapy after TA were also registered. RESULTS: A total of 361 patients (244 females, 117 males, median age 58 years, IQR 46-70 years) were included. Nodule volume was significantly reduced at all time points (p < 0.001) (median volume reduction 58% at 6-month and 60% at 12-month). Serum TSH values increased significantly at all time points. After TA, anti-thyroid therapy was withdrawn in 32.5% of patients at 2 months, in 38.9% at 6 months, and in 41.3% at 12 months. A significant difference in the rate of patients who withdrawn medical therapy at 12 months was registered between small (< 10 mL) (74%), medium (49%), or large (> 30 mL) nodules (19%). A single major complication occurred (0.25%). Additional treatments were needed in 34/361 (9.4%) of cases including 4 (1.1%) surgical treatment. CONCLUSIONS: Image-guided thermal ablation offers a further safe and effective therapeutic option in patients with AFTN. Clinical outcomes are significantly more favorable in small than in large size AFTN. KEY POINTS: • Thermal ablations (TA) can be safely and effectively used in patients with autonomously functioning thyroid nodules (AFTN). • TA results in a clinically significant nodule volume reduction that is paralleled by TSH level normalization and anti-thyroid drug therapy discontinuation (after TA anti-thyroid therapy was withdrawn in 41.3% at 12 months). • Clinical outcomes after TA are more favorable in small nodules, and when a large amount of thyroid nodule tissue is ablated.

Percutaneous Ultrasound-Guided Laser Ablation of Benign Thyroid Nodules: Results of 10-Year Follow-Up in 171 Patients.

CONTEXT: Percutaneous, ultrasound-guided laser ablation is effective in nodular thyroid disease. OBJECTIVE: The aim of this study was to evaluate the long-term (10-year) efficacy and safety of laser ablation in the treatment of benign thyroid nodules. METHODS: From 2009 to 2010, 171 patients received a single session of laser ablation. Evaluation of nodule volume was performed before treatment, at 6 months, and every year. RESULTS: Technique efficacy was achieved in 92% of patients at 1 year. Median nodule volume significantly decreased from 16.7 mL (range, 11.0-97.0 mL) at baseline to 5.0 mL (range, 4.1-32.0 mL) at 1 year, a volume reduction ratio (VRR) of 68%. The benefit of the treatment was durable (P < 0.001 vs baseline at all timepoints), with a VRR of 59% after 10 years. No cases of nodule regrowth > 50% were observed at 1 year, although such cases did occur after 4 years (n = 3; 1.7% of the overall cohort) and 7 years (n = 8; 4.7%). There were no further cases of regrowth beyond 7 years. When patients were stratified according to baseline nodule volume (< 15 mL, 15-25 mL, or > 25 mL), durable results were observed across all 3 categories, with the largest, most prolonged effect observed in patients with nodules < 15 mL. Treatment was well tolerated, with only minor, transient complications of fever and local pain, and 98% of patients willing to recommend the treatment. CONCLUSION: Percutaneous, ultrasound-guided laser ablation of benign thyroid nodules provides long-term benefits and the treatment is well tolerated.

Minimally-invasive treatments for benign thyroid nodules: a Delphi-based consensus statement from the Italian minimally-invasive treatments of the thyroid (MITT) group.

Benign thyroid nodules are a common clinical occurrence and usually do not require treatment unless symptomatic. During the last years, ultrasound-guided minimally invasive treatments (MIT) gained an increasing role in the management of nodules causing local symptoms. In February 2018, the Italian MIT Thyroid Group was founded to create a permanent cooperation between Italian and international physicians dedicated to clinical research and assistance on MIT for thyroid nodules. The group drafted this list of statements based on literature review and consensus opinion of interdisciplinary experts to facilitate the diffusion and the appropriate use of MIT of thyroid nodules in clinical practice. (#1) Predominantly cystic/cystic symptomatic nodules should first undergo US-guided aspiration; ethanol injection should be performed if relapsing (level of evidence [LoE]: ethanol is superior to simple aspiration = 2); (#2) In symptomatic cystic nodules, thermal ablation is an option when symptoms persist after ethanol ablation (LoE = 4); (#3) Double cytological benignity confirmation is needed before thermal ablation (LoE = 2); (#4) Single cytological sample is adequate in ultrasound low risk (EU-TIRADS ≤3) and in autonomously functioning nodules (LoE = 2); (#5) Thermal ablation may be proposed as first-line treatment for solid, symptomatic, nonfunctioning, benign nodules (LoE = 2); (#6) Thermal ablation may be used for dominant lesions in nonfunctioning multinodular goiter in patients refusing/not eligible for surgery (LoE = 5); (#7) Clinical and ultrasound follow-up is appropriate after thermal ablation (LoE = 2); (#8) Nodule re-treatment can be considered when symptoms relapse or partially resolve (LoE = 2); (#9) In case of nodule regrowth, a new cytological assessment is suggested before second ablation (LoE = 5); (#10) Thermal ablation is an option for autonomously functioning nodules in patients refusing/not eligible for radioiodine or surgery (LoE = 2); (#11) Small autonomously functioning nodules can be treated with thermal ablation when thyroid tissue sparing is a priority and ≥80% nodule volume ablation is expected (LoE = 3).

A single session of laser ablation for toxic thyroid nodules: three-year follow-up results.

PURPOSE: To confirm the effectiveness of laser ablation on toxic nodules in a large population with three years of follow-up. MATERIAL AND METHODS: Between 2009 and 2014, we treated 82 patients with hyperthyroidism related to the presence of a toxic nodular goitre. Patients were pre-treated pharmacologically with methimazole prior to single session of laser ablation (LA) and then followed up every 3 months with FT4 and TSH blood tests as well as ultrasound examination of the nodules treated. RESULTS: All patients responded to the treatment. The median nodule volume decreased from 12 ml (range 5-118 ml) to 5 ml (range 1.2-40 ml) after three years (p < 0.001). The percentage of patients who discontinued methimazole therapy was reduced by increasing the initial volume of the toxic nodule. In nodules with a volume less than 5 ml, all patients were able to suspend methimazole; this percentage was reduced to 90.2% in nodules with a volume between 5 and 15 ml, 61.1% in those with volume 15-25 ml and only 28.5% in nodules larger than 25 ml. We had no major complications but only moderate pain and fever in the evening, a few hours after ablation therapy in 10% of treated patients. CONCLUSIONS: Single session of LA of toxic thyroid nodules is effective and safe, especially in nodules with a volume under 15 ml.

A comparison of laser with radiofrequency ablation for the treatment of benign thyroid nodules: a propensity score matching analysis.

PURPOSE: To compare technique efficacy and safety of laser ablation (LA) and radiofrequency ablation (RFA) in treatment of benign thyroid nodules. MATERIALS AND METHODS: Institutional review board approval was obtained, and patients' consent was waived. 601 nodules were treated from May 2009 to December 2014 at eight centres, 449 (309 females, age 57 ± 14 years) with LA and 152 (107 females, age 57 ± 14 years) with RFA. A matched cohort composed of 138 patients from each group was selected after adjustment with propensity score matching. Factors influencing volume reduction at 6 and 12 months and complications were evaluated. RESULTS: No significant differences were observed in the baseline characteristics between groups after propensity score matching adjustment. Mean nodule reduction at 6 and 12 months was -67 ± 19% vs. -57 ± 21% (p < 0.001) - 70 ± 19% vs. -62 ± 22% (p = 0.001) in LA group and in RFA group, respectively. Nodules with volume >30 mL had significantly higher percentage volume reduction at 6 and 12 months (-69 ± 19 vs. -50 ± 21, p = 0.001) and (-73 ± 18 vs. -54 ± 23 8, p = 0.001) in the LA group than in the RFA group, respectively. In both groups, operator's skills affected the results. Major complications occurred in 4 cases in each group (p = 0.116) Conclusions: LA and RFA showed nearly similar outcome but LA was slightly more effective than RFA in large nodules. Operator's skills could be crucial in determining the extent of nodule volume reduction regardless of the used technique.

Thyroid nodule morphology affects the efficacy of ultrasound-guided interstitial laser ablation: a nested case-control study.

PURPOSE: The literature reports a wide range of percentages of ablation in the treatment of thyroid nodules. The aim of this nested case-control study was to evaluate whether the different morphological (well-defined vs. agglomerate) characteristics of nodules affect the success rate. MATERIALS AND METHODS: We selected 20 patients with a single and /or dominant well-defined nodule (group 1) and 20 with a nodular formation resulting from the fusion of multiple nodules (group 2). All the nodules were treated by the laser method receiving the same energy. RESULTS: At 6 months, patients in group 1 showed a greater decrease in volume than those in group 2. These differences were more evident after 12 months. CONCLUSIONS: Our study demonstrates that the efficacy of laser treatment can be predicted by nodule morphology and contributes to explaining the wide differences in the percentages of ablation reported in literature.

The administration of anesthetic in the thyroid pericapsular region increases the possibility of side effects during percutaneous laser photocoagulation of thyroid nodules.

BACKGROUND AND OBJECTIVE: Nodular thyroid disease is very frequent in iodine-deficient areas affecting at least 50% of the population. Percutaneous laser ablation (LA) represents an effective method and an alternative to conventional surgery. Since the first description of the LA methodology for thyroid nodules, various studies have suggested some modifications to increase the percentage of volume reduction of the nodules. One of these alternatives involves the injection of anesthetic in the pericapsular thyroid space with detachment of the capsule itself from the surrounding tissue. The aim of this study was to retrospectively evaluate whether using local anesthetic during LA is more effective in reducing volume size of treated nodules, and whether it causes fewer side effects than using no local anesthesia. STUDY DESIGN: A retrospective analysis was conducted on 100 LA procedures performed on 100 patients between January 2009 and December 2011. The patients were divided into two groups: Group A (n = 50) received Lidocaine around the capsule of the thyroid nodule and Group B (n = 50) did not receive any local anesthetic treatment. Before treatment, the median volume size of the nodules of the two groups was similar. RESULTS AND CONCLUSIONS: The results of our study demonstrate that the injection of local anesthetic does not help reduce nodule volume and that side effects (fever and pain) increase about threefold in the early hours following LA treatment. Thus, we do not recommend local anesthesia before LA of thyroid nodules.

Ultrasound-guided interstitial laser ablation for thyroid nodules is effective only at high total amounts of energy: results from a three-year pilot study.

OBJECTIVE: According to cross-sectional surveys, the prevalence of nontoxic nodular goiter appears to be higher in the adult population. Surgical intervention is indicated for the following: (a) progressive goiter growth, (b) compression of organs such as the trachea and esophagus, and (c) significant aesthetic disfigurement. Ultrasound-guided laser photocoagulation for the treatment of benign thyroid nodules is a viable alternative to traditional surgery. However, studies that have appeared in literature since the introduction of ultrasound-guided laser photocoagulation for the treatment of benign thyroid nodules report contradictory data concerning the energy required for nodule ablation. The aim of the present trial was to evaluate retrospectively the efficacy of percutaneous laser thermal ablation in 2 groups of patients, one treated with low, and the other with high, total amount of energy. DESIGN: Forty euthyroid patients were treated with 1 session of percutaneous laser photocoagulation treatment at low (median = 71 J/mL; 20 patients) and high (median = 578 J/mL; 20 patients) energy. The volume of the nodules was measured by the same investigator, blinded for treatment, using the ellipsoid formula before treatment, at 2, 4, 8, and 30 weeks, and every 6 months for 3 years thereafter. RESULTS: Thyroid nodule ablation is effective over time only if a sufficient amount of energy (>400-500 J/mL for the nodular tissue to be treated) is given, although it incurs proportionate side effects. CONCLUSIONS: Percutaneous laser thermal ablation is a viable alternative to traditional surgery for the treatment of benign nodular thyroid disease only if a sufficient amount of energy is delivered.

Association of genetic polymorphisms and autoimmune Addison's disease.

Autoimmune Addison's disease (AAD) is a complex genetic disease that results from the interaction of a predisposing genetic background with as yet unknown environmental factors. The disease is marked by the appearance of circulating autoantibodies against steroid 21-hydroxylase. Mutations of the autoimmune regulator gene are responsible for the so-called autoimmune polyendocrine syndrome type I (APS I), of which AAD is a major disease component. Among genetic factors for isolated AAD and APS II, a major role is played by HLA class II genes: HLA-DRB1 0301-DQA1 0501-DQB1 0201 and DRB1 04-DQA1 0301-DQB1 0302 are positively, and RB1 0403 is negatively, associated with a genetic risk for AAD. The MHC class I chain-related gene A allele 5.1 is strongly and positively associated with AAD. Other gene polymorphisms contributing to genetic risk for AAD are MHC2TA, the gene coding for class II transactivator, the master regulator of class II expression, cytotoxic T lymphocyte antigen-4, PTPN22 and the vitamin D receptor.

MICA A8: a new allele within MHC class I chain-related A transmembrane region with eight GCT repeats.

Analysis of the MICA gene revealed a trinucleotide repeat (GCT) microsatellite polymorphism within the transmembrane region. So far, seven alleles of the exon 5 of the MICA gene, which consist of 4, 5, 6, 7, 9, and 10 repetitions of GCT or five repetitions of GCT with an additional nucleotide insertion (GGCT), have been identified. These alleles have been accordingly named A4, A5, A6, A7, A9, A10, and A5.1, and the sizes are, respectively, 179 bp, 182 bp, 186 bp, 189 bp, 194 bp, 197 bp, and 185 bp. We analyzed 1100 Italian subjects for MICA exon 5 microsatellite polymorphism. A new peak corresponding to 191-bp size was observed in one individual, and we confirmed the presence of new polymorphism in exon 5 by sequencing, which consisted of eight GCT repeats. We named this allele, as a current nomenclature, MICA8.

Genetic polymorphism of chemokine receptors CCR2 and CCR5 in Swedish cervical cancer patients.

Chemokines are chemotactic cytokines that orchestrate leukocyte trafficking in tissues, thus, playing an important role in regulation of immunological processes. The aim of this study was to investigate the association of human papillomavirus (HPV) infection and cervical cancer with two DNA polymorphisms of the chemokine receptors CCR5-delta32 and CCR2-64I. The study material consisted of 50 cervical intraepithelial neoplasia (CIN) cases and 50 of age and sampling-date matched controls, 100 invasive cervix cancer cases and 100 of their corresponding matched disease-free controls. Pyrosequencing was employed to genotype the CCR2-64I polymorphism. CCR5-delta32 was genotyped using standard PCR fragment length analysis. The frequencies of CCR2 and CCR5 genotypes from 150 patients and 150 healthy controls were representative of the general population according to the Hardy-Weinberg equilibrium analysis. Risk association was computed with conditional logistic regression analysis. HPV-positive individuals with the rare CCR5deelta32/delta32 genotype have a risk of 4.58 (CI = 0.40-52.64, p-value = 0.045) compare to HPV negative group. The delta-32 mutation on the CCR locus is imperceptibly associated with increased risk of HPV infection. In total, cervical neoplasia was not associated with genetic polymorphism of CCR2 and CCR5.

Exercise and diabetes.

Physical activity activates has acute and chronic effects on glucose, lipid and protein metabolism. In type 1 diabetic subjects, the lack of the physiological inhibition of insulin secretion during exercise results in a potential risk of hypoglycemia. On the other hand, exercise-induced activation of counterregulatory hormones might trigger an acute metabolic derangement in severe insulin-deficient subjects. Thus, diabetic patients, before starting exercise sessions, must be carefully educated about the consequences of physical activity on their blood glucose and the appropriate modifications of diet and insulin therapy. Long-term effects of regular exercise are particularly advantageous for type 2 diabetic patients. Regular aerobic exercise reduces of visceral fat mass and body weight without decreasing lean body mass, ameliorates insulin sensitivity, glucose and blood pressure control, lipid profile and reduces the cardiovascular risk. For these reasons, regular aerobic physical activity must be considered an essential component of the cure of type 2 diabetes mellitus. In this regard, individual behavioral strategies have been documented to be effective in motivating sedentary type 2 diabetic subjects to the adoption and the maintenance of regular physical activity.

MHC2TA single nucleotide polymorphism and genetic risk for autoimmune adrenal insufficiency.

CONTEXT: The polymorphism of class II HLA genes modulates the genetic risk for several endocrine autoimmune diseases. The constitutive class II expression on antigen-presenting cells is under the control of the MHC class II transactivator, encoded by the MHC2TA gene, which is mapped to chromosome 16p13. The MHC2TA -168 A-->G single nucleotide polymorphism (rs3087456) has been suggested to confer susceptibility to some autoimmune diseases. DESIGN: With the aim of testing whether this MHC2TA single nucleotide polymorphism is independently associated with autoimmune Addison's disease (AAD) and/or modulates the genetic risk conferred by DRB1-DQA1-DQB1 haplotypes, we analyzed DNA samples from 128 AAD patients and 406 healthy control subjects from continental Italy. RESULTS: Frequency of allele G of MHC2TA was significantly increased among AAD patients (39% alleles), compared with 29% in healthy controls (P = 0.003). Similarly, the frequency of AG+GG genotypes was significantly higher among AAD patients than among healthy control subjects, in both a codominant (P = 0.012) and a G-dominant model (P = 0.018). Multivariate logistic regression analysis showed that MHC2TA AG+GG continued to be positively associated with genetic risk for AAD (P = 0.028, odds ratio = 1.72, 95% confidence interval = 1.06-2.78), after correction for DRB1*03-DQA1*0501-DQB1*0201, DRB1*04 (not 0403)-DQA1*0301-DQB1*0302 and DRB1*0403. Similar results were obtained when the number of G alleles was included in the model (P = 0.004; odds ratio = 1.65, 95% confidence interval = 1.17-2.32). CONCLUSIONS: Our study provides the first demonstration of the association of the polymorphism of the MHC2TA gene with genetic risk for AAD that appears to be independent from the well-known association with the polymorphism of HLA class II genes.

Retrovirus-like long-terminal repeat DQ-LTR13 and genetic susceptibility to type 1 diabetes and autoimmune Addison's disease.

Controversial data are available on the association between the retrovirus-like long-terminal repeat (LTR) DQ-LTR13 and genetic susceptibility to type 1 diabetes and other autoimmune diseases. We analyzed DNA samples from 315 type 1 diabetic patients, 166 autoimmune Addison's disease (AAD) patients, 1,054 healthy subjects, and 144 families of type 1 diabetic offspring. DQ-LTR13 was more frequent among patients than healthy subjects (P(c) < 0.0006), and a preferential transmission of DQB1*0302-LTR13(+) from parents to type 1 diabetic offspring was observed. DQ-LTR13 was in linkage disequilibrium (LD) with DQB1*0302 but not DQB1*0201. The presence of DQ-LTR13 increased the odds ratio of DQB1*0302 2.9- to 3.2-fold for type 1 diabetes and AAD. DRB1*0403 was absent in all of the 169 DRB1*04-positive patients but present in 27% (34 of 127) DRB1*04-positive healthy subjects (P(c) < 0.001). DQ-LTR13 was detected in 1 of 34 (3%) DRB1*0403-positive healthy subjects and 36 of 93 (39%) individuals carrying another DRB1*04 allele (P(c) = 0.002). Multivariate logistic regression analysis revealed that DQ-LTR13 is not independently associated with type 1 diabetes and AAD after correction for DQB1*0302 and DRB1*0403. Conversely, DQB1*0201, DQB1*0302, DRB1*0401, and DRB1*0403 were all significantly associated with disease risk also after correction for DQ-LTR13. We provide conclusive evidence that the genetic association of DQ-LTR13 with type 1 diabetes and AAD is primarily due to a LD with DQB1*0302 and DRB1*0403.

Lack of association of CCR2-64I and CCR5-Delta 32 with type 1 diabetes and latent autoimmune diabetes in adults.

It is well known that type 1 diabetes mellitus (T1DM) is a complex genetic disease resulting from the autoimmune destruction of pancreatic beta cells. Several genes have been associated with susceptibility and/or protection for T1DM, but the disease risk is mostly influenced by genes located in the class II region of the major histocompatibility complex. The attraction of leukocytes to tissues is essential for inflammation and the beginning of autoimmune reaction. The process is controlled by chemokines, which are chemotactic cytolines. Some studies have shown that CCR2-64I and CCR5-Delta 32 might be important for protection of susceptibility to some immunologically-mediated disorders. In the present study, we demonstrate the lack of association between CCR2-64I and CCR5-Delta 32 gene polymorphism and TIDM and we describe a new method for a simple and more precise genotyping of the CCR2 gene.

CTLA-4 gene polymorphism contributes to the genetic risk for latent autoimmune diabetes in adults.

Latent autoimmune diabetes in adults (LADA) is identified by the presence of GAD65 autoantibodies in diabetic patients who do not require insulin treatment for at least six months after the diagnosis. Previous studies have shown that the risk for LADA, similarly to type 1 diabetes mellitus (T1DM), is increased in subjects carrying the HLA-DRB1*03-DQA1*0501-DQB1*0201 and/or HLA-DRB1*04-DQA1*0301-DQB1*0302 haplotypes. In the present study, we investigated the association between LADA and the CTLA-4 A/G polymorphism, another gene polymorphism associated with T1DM and other autoimmune diseases. The heterozygous A/G genotype was significantly more frequent among 80 LADA (69%) than among 85 healthy subjects of similar age and geographical provenience (47%) (OR = 2.47, corrected P = 0.023). Conversely, the homozygous A/A genotype was significantly less frequent in LADA subjects than in healthy controls (26% vs. 47%, OR = 0.4, corrected P = 0.028). The results of our study show that LADA is positively associated with the CTLA-4 A/G genotype, similarly to T1DM, thus providing further supporting evidence of the autoimmune origin of this form of diabetes mellitus of the adult.