Solving the mystery of HBV-related mixed cryoglobulinemia: potential biomarkers of disease progression.

OBJECTIVES: The biomarkers of an immunological dysregulation due to a chronic HBV infection are indeed understudied. If untreated, this condition may evolve into liver impairment co-occurring with extrahepatic involvements. Here, we aim to identify a new panel of biomarkers [including immunoglobulin G (IgG) subclasses, RF, and Free Light Chains (FLCs)] that may be useful and reliable for clinical evaluation of HBV-related cryoglobulinemia. METHODS: We retrospectively analysed clinical data from 44 HBV-positive patients. The patients were stratified (according to the presence/absence of mixed cryoglobulinemia) into two groups: 22 with cryoglobulins (CGs) and 22 without CGs. Samples from 20 healthy blood donors (HDs) were used as negative controls. Serum samples were tested for IgG subclasses, RF (-IgM, -IgG, and -IgA type), and FLCs. RESULTS: We detected a strikingly different distribution of serum IgG subclasses between HDs and HBV-positive patients, together with different RF isotypes; in addition, FLCs were significantly increased in HBV-positive patients compared with HDs, while no significant difference was shown between HBV-positive patients with/without mixed cryoglobulinemia. CONCLUSION: The immune-inflammatory response triggered by HBV may be monitored by a peculiar profile of biomarkers. Our results open a new perspective in the precision medicine era; in these challenging times, they could also be employed to monitor the clinical course of those COVID-19 patients who are at high risk of HBV reactivation due to liver impairment and/or immunosuppressive therapies.

Systemic Bone Density at Disease Onset Is Associated With Joint Erosion Progression in Early Naive to Treatment Rheumatoid Arthritis: A Prospective 12-Month Follow-Up Open-Label Study.

Objectives: Osteoporosis and bone erosions are hallmarks of rheumatoid arthritis (RA) since disease onset is underpinned by the inflammatory burden. In this observational study, we aimed to dissect the putative RA-related parameters and bone-derived biomarkers associated with systemic and focal bone loss at disease onset and with their progression. Methods: One-hundred twenty-eight patients with early rheumatoid arthritis (ERA) were recruited at disease onset. At study entry, demographic, clinical, and immunological parameters were recorded. Each ERA patient underwent plain X-rays of the hands and feet at study entry and after 12 months to assess the presence of erosions. After enrollment, each patient was treated according to the recommendations for RA management and followed up based on a treat-to-target (T2T) strategy. At baseline, blood samples for soluble biomarkers were collected from each patient, and plasma levels of osteoprotegerin (OPG), receptor activator of nuclear factor κB ligand (RANKL), Dickkopf-1 (DKK1), and interleukin 6 (IL-6) were assessed by enzyme-linked immunosorbent assay (ELISA). Seventy-one ERA patients underwent bone mineral density (BMD) measurement at the left femoral neck and second to fourth lumbar spine vertebrae (L2-L4) by dual-energy X-ray absorptiometry (DXA). Results: Among the whole cohort, 34 (26.6%) ERA patients with bone erosions at study entry had a higher disease activity (p = 0.02) and IL-6 plasma levels (p = 0.03) than non-erosive ones. Moreover, at DXA, 33 (46.5%) ERA patients had osteopenia, and 16 (22.5%) had osteoporosis; patients with baseline bone erosions were more likely osteopenic/osteoporotic than non-erosive ones (p = 0.03), regardless of OPG, RANKL, and DKK1 plasma levels. Obese ERA patients were less likely osteopenic/osteoporotic than normal weight ones (p = 0.002), whereas anti-citrullinated protein antibodies (ACPA) positive ERA patients were more likely osteopenic/osteoporotic than ACPA negative ones (p = 0.034). At logistic regression analysis, baseline Disease Activity Score measured on 44 joints (DAS44) [OR: 2.46 (1.11-5.44)] and osteopenic/osteoporosis status [OR: 7.13 (1.27-39.94)] arose as independent factors of erosiveness. Baseline osteopenic/osteoporotic status and ACPA positivity were associated with bone damage progression during the follow-up. Conclusions: Bone erosions presence is associated with systemic bone loss since the earliest phases of RA, suggesting that the inflammatory burden and autoimmune biology, underpinning RA, represent crucial enhancers of bone remodeling either locally as at systemic level.

Thyroid hormones modulate uric acid metabolism in patients with recent onset subclinical hypothyroidism by improving insulin sensitivity.

Some evidence suggests a relationship between thyroid dysfunction and uric acid (UA) metabolism, but the potential influential role of thyroid hormones on UA metabolism is still debated. This report was designed to evaluate the influential role of levothyroxine (L-T4) replacement therapy on circulating levels of UA in patients with recent onset post-thyroidectomy subclinical hypothyroidism. Circulating levels of thyroid hormones, UA and other metabolic parameters were assessed in 155 recently thyroidectomized patients (131 females, mean age 51.1 ± 12.7 years) at baseline (5-7 day after surgery) and after 2 months under replacement therapy with L-T4. At baseline, circulating levels of thyroid hormones were indicative of a subclinical hypothyroidism (TSH 8.2 ± 5.1 mU/mL, FT3 2.1 ± 0.7 pg/mL, FT4 9.2 ± 3.4 pg/mL). The mean serum UA concentration was 5.0 ± 1.3 mg/dL, while the prevalence of hyperuricemia, defined by serum UA levels > 6 mg/dL, was 22.6%. Serum UA levels at baseline were significantly correlated with HOMA-IR index (r = 0.475, p < 0.0001). After 2 months under the replacement therapy with L-T4, both serum UA levels (- 1.2 ± 0.9 mg/dL, p < 0.0001 vs. baseline) and HOMA-IR (- 0.3 ± 1.5 mmol/L, p = 0.0328 vs. baseline) significantly decreased. Multivariate regression analysis revealed that changes in HOMA-IR explained 23% of the variations of serum UA levels under L-T4 replacement therapy (ß = 0.295, p < 0.0001, R2 = 0.230). Our study suggests that thyroid hormones could modulate UA metabolism in patients with recent onset subclinical hypothyroidism likely by improving insulin sensitivity.

Anti-Müllerian hormone serum levels in systemic lupus erythematosus patients: Influence of the disease severity and therapy on the ovarian reserve.

PURPOSE: Systemic lupus erythematosus (SLE) mainly affects childbearing age women and pharmacological treatments may negatively influence the ovarian reserve. Anti-Müllerian hormone (AMH) could be a good biomarker for ovarian reserve. METHODS: AMH serum levels were assessed in 86 consecutive SLE female patients with regular menstrual cycle compared with 44 aged matched healthy controls. Clinical and demographic characteristics, disease duration, pattern of organ involvement, and previous and current therapies were recorded. RESULTS: AMH levels were comparable between patients and controls (4.2 ± 3.1 ng/ml vs. 5.0 ± 3.1 ng/ml, p = 0.21). According to disease severity, AMH levels were lower in SLE patients with major organ involvement than in controls (3.8 ± 2.7 ng/ml vs. 5.0 ± 3.1 ng/ml, p = 0.08); no difference was found between SLE patients with mild organ involvement (4.5 ± 3.4 ng/ml) and controls (p = 0.43). Grouping patients based on the pharmacological treatments, AMH serum levels did not differ among SLE patients treated with antimalarials only (4.7 ± 3.3 ng/ml), conventional disease-modifying antirheumatic drugs (cDMARDs) only (4.8 ± 3.2 ng/ml), cDMARDs and antimalarials (3.9 ± 2.9 ng/ml) or cyclophosphamide (CYC) only (4.9 ± 3.9 ng/ml), compared to controls, but patients sequentially treated with cDMARDs and CYC, had significantly lower AMH serum levels than controls (p = 0.01). CONCLUSIONS: SLE patients showed comparable AMH levels than controls, however, a reduction of the ovarian reserve was associated with sequentially therapy with CYC and cDMARDs and with the disease severity. AMH could be a sensitive and specific biomarker of ovarian reserve in SLE and it could be useful for therapeutic strategy and family planning.

Correction to: Anti-Müllerian hormone serum levels in systemic lupus erythematosus patients: influence of the disease severity and therapy on the ovarian reserve.

The original version of this article unfortunately contained a mistake in given and family names of all the authors.

Comparative study between the effects of replacement therapy with liquid and tablet formulations of levothyroxine on mood states, self-perceived psychological well-being and thyroid hormone profile in recently thyroidectomized patients.

Following thyroid surgery, levothyroxine therapy is used to replace deficient thyroid hormones and prevent postoperative thyroid hypofunction. We compared the effects of replacement therapy with either liquid or tablet formulation of levothyroxine on mood states, self-perceived mental well-being and thyroid hormone profile in recently thyroidectomized patients. Profile of mood states, General Heath Questionnaire 12-items and thyroid hormone profile were assessed in recently (5-7 days) thyroidectomized patients at baseline and 2 months after randomization to replacement therapy with either liquid (n = 77) or tablet (n = 78) formulation of levothyroxine. After 2 months under levothyroxine replacement treatment, significant improvements of Positive Affect Scale (p < 0.001) and Negative Affect Scale (p < 0.001) of Profile of mood states, as well as of General Heath Questionnaire 12-items (p < 0.001) were observed in the study population. However, there were greater variations observed in patients assigned to liquid levothyroxine formulation in comparison to those who were assigned to levothyroxine in the form of tablet (time × treatment interaction: Positive Affect Scale of Profile of mood states, p = 0.030; Negative Affect Scale of Profile of mood states, p < 0.0001; General Heath Questionnaire 12-items, p = 0.003). As expected, circulating TSH levels significantly decreased (p <0.001) while FT3 and FT4 levels significantly increased (p < 0.0001 for both) under levothyroxine replacement therapy. These changes were significantly greater in patients treated with liquid levothyroxine formulation (time × treatment interaction: TSH, p = 0.011; FT3, p = 0.016; FT4, p = 0.028). Our data indicate a greater efficacy of liquid formulation of levothyroxine in ameliorating mood states and self-perception of mental well-being and thyroid hormone profile after 2 months of replacement therapy in recently thyroidectomized patients.

Androgen and prolactin (Prl) levels in systemic sclerosis (SSc): relationship to disease severity.

Testosterone (T), sex hormone-binding globulin, (SHBG), dehydroepiandrosterone sulfate (DHEAS), and prolactin (Prl) serum levels were measured by electrochemiluminescense immunoassay (ECLIA) in 39 patients with systemic sclerosis (SSc) and compared with serum hormonal levels in control subjects matched for sex and reproductive status. A possible relationship with disease duration and disease severity was examined. Our data show an altered androgen and prolactin (Prl) status in SSc patients, in most cases related to disease duration and disease severity score. We can hypothesize that hormonal dysregulation is a consequence of the chronicity of the disease. The altered hormonal status could result in relative immunological hyperactivity contributing to enhance tissue damage and disease severity.