Genetic variants of chemokine receptor CCR7 in patients with systemic lupus erythematosus, Sjogren's syndrome and systemic sclerosis.

BACKGROUND: The chemokine receptor CCR7 is a key organizer of the immune system. Gene targeting in mice revealed that Ccr7-deficient animals are severely impaired in the induction of central and peripheral tolerance. Due to these defects, Ccr7-deficient mice spontaneously develop multi-organ autoimmunity showing symptoms similar to those observed in humans suffering from connective tissue autoimmune diseases. However, it is unknown whether mutations of CCR7 are linked to autoimmunity in humans. RESULTS: DNA samples were collected from 160 patients suffering from connective tissue autoimmune disease (Sjogren's syndrome, n = 40; systemic lupus erythematosus, SLE, n = 20 and systemic sclerosis, n = 100) and 40 health subjects (n = 40). All participants in this study were of German descent. Samples were screened for single nucleotide polymorphisms (SNP) by sequencing the coding region of the CCR7 gene as well asthe exon flaking intron sites and parts of the regions encoding for the 5'- and 3'-UTR. CCR7 variants were rare. We identified six different sequence variants, which occurred in heterozygosis. The identified SNP were observed at position -60 C/T (observed 1x), +6,476 A/G (7x), +6,555 C/T (15x), +6,560 C/T (6x), +10,440 A/G (3x) and +11,475 C/A (1x). Four of these variants (+6,476 A/G, +6,555 C/T, +6,560 C/T and +10,440 A/G) display allelic frequencies between 1% and 5 % and were present in both patients and control groups. The variants +6,476 A/G, +6,555 C/T, +6,560 C/T are located in the intron 2, while the +10,440 A/G variant corresponds to a silent mutation in exon 3. The variants -60 C/T and +11,475 C/A which are located at the 5'-UTR and 3-UTR respectively, display allelic frequencies below 1%. No correlation between these variants and the autoimmune diseases investigated could be observed. However, reporter gene expression assay demonstrated that the mutation at the -60 C/T position in homozygosis leads to reduced luciferase activity. CONCLUSION: These results suggest that variants of CCR7 gene occur at an extremely low frequency in the German population and that neither Sjogren's syndrome, systemic lupus erythematosus, nor systemic sclerosis are associated with these variants. Nevertheless, the decreased luciferase activity observed in cells transfected with the promoter region bearing the -60 C/T mutation suggests that this CCR7 variant could potentially lead to increased susceptibility to autoimmunity.

[The pedicled groin flap for defect closure of the hand]. / Der gestielte Leistenlappen zur Defektdeckung an der Hand.

OBJECTIVE: Soft-tissue defect closure of the volar and dorsal aspect of the hand and lower arm with a maximum defect size of 10 × 25 cm. INDICATIONS: Soft-tissue defects of the entire palm and dorsum of the hand and lower arm with a maximum defect size of 10 × 25 cm. CONTRAINDICATIONS: Polytraumatized patients presenting with concomitant life-threatening injuries. In these cases one should perform the definite defect closure secondary after cardiovascular stabilization. Scars and vascular injury at the donor site. Lack of vascularity and necrosis of implantation site. Poorly vascularized recipient site (e.g. after radiation) Infection and necrosis at the donor and/or recipient site. Prior operations of the groin with impairment of the vasculature. Noncompliant patient. SURGICAL TECHNIQUE: Landmarks are the femoral artery, inguinal ligament, anterior superior iliac spine, and sartorius muscle. The superior and inferior border of the flap should be orientated parallel to the inguinal ligament. The longitudinal axis of the flap is parallel to the superficial circumflex iliac artery, which is partially located superior to the inguinal ligament. One third of the flap is located superior, and two thirds inferior, to the inguinal ligament. Flap dissection starts at the lateral border without including the fascia. Identification of the lateral border of the sartorius muscle, incision of its fascia and inclusion of the fascia into flap dissection in order to preserve the vessel. If a long flap pedicle is favored, flap dissection is continued to the source of the superficial circumflex iliac artery. Primary closure of the donor site and, finally, inset of the flap. A tubed pedicle protects the vessels and simplifies the ischemic preconditioning during the postoperative phase. According to the flap size, the donor site closure is either primary or split-thickness skin grafting is necessary at the lateral aspect of the donor site. The mean duration of the procedure is 120 min in a teaching hospital (own data). POSTOPERATIVE MANAGEMENT: The patient should be mobilized as early as possible. Dressings and flap monitoring should be performed daily. Ischemic preconditioning by applying a tourniquet starts after 10-14 days. The ischemic period is increased continuously from 3 × 5 min/d in the beginning to 3 × 1 h/d before flap dissection. Flap dissection of the pedicle is performed after 3 weeks. The residual donor site is closed, while the distal pedicle is left untrimmed and closed secondarily a few days later to allow for sufficient venous drainage. Finally, defect closure can be completed after demarcation of the pedicle. RESULTS: In a 3-year period, defect closure with a pedicled groin flap was performed in 14 patients. Indications for this procedure were the following: thumb reconstruction for lengthening and defect closure after amputation and burn injury, soft-tissue reconstruction of the dorsum of the hand after decollement and infection, soft-tissue reconstruction of the distal part of the lower arm, wrist and palm after complex and combined trauma, and plastic reconstructive preservation of multiple fingers with subsequent phalangealization and syndactyly release, respectively. In all patients, complete soft-tissue coverage and flap survival could be achieved. The functional and aesthetic result was satisfactory in all cases.