Immunoglobulin Preparations Can Mislead Clinical Decision-Making in Follow-Up of Differentiated Thyroid Cancer.

OBJECTIVE: Intravenous and subcutaneous immunoglobulins are commonly used for immune substitution or as immune modulators in a variety of inflammatory and autoimmune disorders. Exogenous thyroid-specific thyroglobulin (Tg) antibodies present in the donor plasma may interfere with the interpretation of measurements of Tg autoantibodies (Tg-Abs) in the recipient's plasma and potentially trigger an immune response in the recipient's immune cells. Levels of antibodies causing bioassay interferences or those leading to clinically relevant changes in patient outcomes are not known. Tg is used as a biomarker in the long-term surveillance of patients with differentiated thyroid cancer (DTC) following total thyroidectomy and radioactive iodine ablation. However, the presence of Tg-Abs in the circulation interferes with Tg measurements. Assessment of levels of Tg-Abs is thus recommended as a part of standard follow-up of DTC together with Tg testing. METHODS: To understand the potential mechanisms and pathophysiologic significance of possible interferences associated with administration immunoglobulin preparations and Tg measurement, we overview the current knowledge on interactions between Tg autoimmunity and immunoglobulin preparations and illustrate diagnostic challenges and perspectives for follow-up of patients with DTC treated with exogenous immunoglobulins. RESULTS: In patients with DTC treated with immunoglobulin preparations, monitoring of thyroid cancer using Tg and Tg-Abs is challenging due to possible analytical interferences through passive transfer of exogenous antibodies from immunoglobulin preparations. CONCLUSION: Analytical interferences must be suspected when a discrepancy exists between clinical examination and diagnostic tests. Collaboration between endocrinologists, biologists, and pharmacologists is fundamental to avoid misdiagnosis and unnecessary medical or radiologic procedures. ABBREVIATIONS: CT = computed tomography; DTC = differentiated thyroid cancer; FNAB = fine-needle aspiration biopsy; HAb = heterophile antibody; IMA = immunometric assay; IVIg = intravenous immunoglobulin; RAI = radioactive iodine; RIA = radioimmunoassay; SCIg = subcutaneous immunoglobulin; Tg = thyroglobulin; Tg-Ab = thyroglobulin autoantibody; Tg-MS = thyroglobulin mass spectrometry; TPO-Ab = thyroid peroxidase autoantibody; TSHR-Ab = thyrotropin receptor autoantibody.

Safety of Intravenous Immunoglobulin (Tegeline®), Administered at Home in Patients with Autoimmune Disease: Results of a French Study.

The efficacy of intravenous immunoglobulins (IVIg) in patients with autoimmune diseases (AID) has been known for several decades. Majority of these patients received IVIg in hospital. A retrospective study was conducted in 22 centers in France to evaluate the feasibility of the administration of Tegeline, an IVIg from LFB Biomedicaments, and assess its safety at home, compared to in hospital, in patients with AID. The included patients were at least 18 years old, suffering from AID, and treated with at least 1 cycle of Tegeline at home after receiving 3 consecutive cycles of hospital-based treatment with Tegeline at a dose between 1 and 2 g/kg/cycle. Forty-six patients with AID, in most cases immune-mediated neuropathies, received a total of 138 cycles of Tegeline in hospital and then 323 at home. Forty-five drug-related adverse events occurred in 17 patients who received their cycles at home compared to 24 adverse events in hospital in 15 patients. Serious adverse events occurred in 3 patients during home treatment, but they were not life-threatening and did not lead to discontinuation of Tegeline. Forty-five patients continued their treatment with Tegeline at home or in hospital; 39 (84.8%) were still receiving home treatment at the end of the study. In conclusion, the study demonstrates the good safety profile of Tegeline administered at home at high doses in patients with AID who are eligible for home administration of Tegeline.

SIMPLE mutation analysis in dominant demyelinating Charcot-Marie-Tooth disease: three novel mutations.

Charcot-Marie-Tooth disease type 1C (CMT1C) is caused by mutations in the small integral membrane protein of the lysosome/late endosome (SIMPLE). We analyzed the coding sequence of SIMPLE in DNA of 53 unrelated cases of dominant demyelinating CMT disease with no mutations in PMP22, GJB1, MPZ, EGR2, and NEFL genes. Four different missense mutations were observed in six families. The mutation Gly112Ser was found in two families confirming its frequent occurrence in SIMPLE mutations. Three novel mutations were also identified: Ala111Gly (two families), Pro135Ser, and Pro135Thr. Familial studies revealed that all carriers of mutations (n = 38), aged from 1 to 78 years, were symptomatic, notably children under 10 years (n = 8). Motor conduction velocities in the median nerve ranked from 16.4 to 32.8 m/s (n = 20). In our series of 968 unrelated dominant demyelinating CMT cases (1992-2005), the percentage of SIMPLE mutations was 0.6 (6/968).

Acitretin-associated thrombotic stroke.

OBJECTIVE: To report a case of thrombotic stroke. The etiology was difficult to identify, but was finally ascribed to psoriatic treatment with acitretin. CASE SUMMARY: Treatment with acitretin was prescribed for a 52-year-old white woman for long-standing psoriasis. Thirty-four days later, she developed nausea, vomiting, vertigo, and headaches, followed by left lateropulsion, which impeded standing and lying. Both neurologic examination and magnetic nuclear imaging indicated a rectangular infarct in the vermis cerebelli and a small bulbar infarct. Time-of-flight magnetic resonance angiography confirmed the presence of a thrombus at the beginning of the left vertebral artery. After heparin-based treatment and physiotherapy, the evolution was favorable. DISCUSSION: Etiology identification of the stroke included cardiogenic pathology and coagulopathy, but acitretin treatment was considered the likeliest explanation. On review of the literature, this seems to be the first case of a thrombotic event associated with acitretin. CONCLUSIONS: Acitretin should be considered as a possible cause of thrombotic stroke; this possibility should be kept in mind when patients taking acitretin develop an unexplained thrombotic event.